The DOI matches its Crossref record; 192 of the 193 references it cites were found in a registry or an index; 107 of the 139 sources its claims cite were checked for support.
Human disease models in drug development
Open accessAbstract
Biomedical research is undergoing a paradigm shift towards approaches centred on human disease models owing to the notoriously high failure rates of the current drug development process. Major drivers for this transition are the limitations of animal models, which, despite remaining the gold standard in basic and preclinical research, suffer from interspecies differences and poor prediction of human physiological and pathological conditions. To bridge this translational gap, bioengineered human disease models with high clinical mimicry are being developed. In this Review, we discuss preclinical and clinical studies that benefited from these models, focusing on organoids, bioengineered tissue models and organs-on-chips. Furthermore, we provide a high-level design framework to facilitate clinical translation and accelerate drug development using bioengineered human disease models. Owing to the high failure rates of the current drug development process, biomedical research is undergoing a paradigm shift towards approaches centred on human disease models. This Review critically discusses translationally relevant examples and defines key milestones for their widespread application. Advances in bioengineering have yielded complex human disease models with high clinical biomimicry and predictability. Human disease models can help unravel disease mechanisms, including for infectious and genetic diseases and cancer. Using appropriate human disease models in the drug development proces…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
53 Own interpretation · 46 Partly supported · 25 Supported · 19 No basis given · 18 No full text of the sources · 4 Own result · 2 Supported so far · 2 Sources not found · 1 Couldn’t confirm · 1 Not checked yet · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“OoCs currently constitute the most promising approach to emulate human diseases in vitro55,61.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
What the sources say
- Partly supportedcites [55] Maschmeyer, I. et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15, 2688–2699 (2015). sourceExperimental — accuracy not yet measured
The Introduction describes organ-on-chip systems as a successful approach to modeling human biology in vitro. The Results and discussion and Conclusions focus on drug absorption, metabolism, excretion, and toxicity testing; they do not establish that these systems model human diseases or are the most promising approach for doing so. Page numbers are unavailable in our copy. (LLM, conf=0.79)
- Partly supportedcites [61] Marx, U. et al. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. Altex 33, 272–321 (2016). sourceExperimental — accuracy not yet measured
Section 4.6 describes organ-on-chip projects for human disease models, and Section 7 envisages Body-on-a-chip systems providing solutions for disease modeling. The paper does not establish that organs-on-chips are currently the most promising in vitro approach; it presents some of these capabilities as future developments. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“OoCs follow a reductionist engineering approach through the targeted and pre-defined design of components”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
What the sources say
- Supportedcites [24] Hofer, M. & Lutolf, M. P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021). source
The Introduction explicitly contrasts self-organizing organoids with organs-on-a-chip, which it describes as based on a reductionist engineering approach. It also says chips are designed to capture selected organ functions by mimicking the tissue elements and microenvironmental properties needed for them. No page number is provided in our copy. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the cell type composition of organoids of the same organ can vary depending on the protocol47, ultimately hindering reproducibility.”
§ Human disease models in drug development > Overview of human disease models > Organoids
What the sources say
- Supportedcites [47] Chichagova, V. et al. Human iPSC differentiation to retinal organoids in response to IGF1 and BMP4 activation is line- and method-dependent. Stem Cell 38, 195–201 (2020). source
The Significance statement reports that two differentiation approaches produced biases toward different retinal cell types, and that the capacity to generate neural retina and retinal pigment epithelium differed across protocols. The Results explicitly frame the comparison as an investigation of reproducibility across iPSC lines. Together, these support the claim for retinal organoids. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“achieving increased biomimicry of native human tissue compared to 2D18,19.”
§ Human disease models in drug development > Overview of human disease models > Bioengineered tissue models
What the sources say
- Partly supportedcites [18] Debels, H., Hamdi, M., Abberton, K. & Morrison, W. Dermal matrices and bioengineered skin substitutes: a critical review of current options. Plast. Reconstr. Surg. Global Open 3, e284 (2015). sourceExperimental — accuracy not yet measured
The Abstract (Conclusions; page unavailable) describes tissue-engineered skin scaffolds as three-dimensional structures, and the Discussion (page unavailable) considers how skin substitutes differ from native human skin. The paper does not compare their resemblance to human tissue with that of 2D cultures, so the claimed improvement over 2D cultures is unsupported. (LLM, conf=0.78)
- Supportedcites [19] Caddeo, S., Boffito, M. & Sartori, S. Tissue engineering approaches in the design of healthy and pathological in vitro tissue models. Front. Bioeng. Biotechnol. 5, 40 (2017). source
The Abstract states that 3D in vitro models can reproduce a tissue or organ more realistically than 2D models. The Scaffolds, Cells, and Stimuli for In Vitro Modeling section identifies these as engineered tissue models, supporting the comparison attributed to this source. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Human disease models can facilitate the process as evidenced by ad hoc systems that emerged during the COVID-19 pandemic1.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [1] Adhikary, P. P., Ul Ain, Q., Hocke, A. C. & Hedtrich, S. COVID-19 highlights the model dilemma in biomedical research. Nat. Rev. Mater. 6, 374–376 (2021). source
The section “COVID-19 highlights the model dilemma in biomedical research” (page not available in our copy) reports that human brain organoids provided insights into which neurons SARS-CoV-2 targets and its neurotoxic effects. This supports the claim that human models helped investigate disease mechanisms during COVID-19. (LLM, conf=0.86)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“they can emulate human (patho)physiology in a more human-like environment49,51,55–57.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
What the sources say
- Supportedcites [49] Lai Benjamin, F. L. et al. Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature. Adv. Funct. Mater. 30, 2000545 (2020). source
The Introduction describes a human-cell organ-on-a-chip system designed to mimic pancreatic tumor stroma and vascular transport. It reports that the system recapitulates a feature of the pancreatic cancer microenvironment, supporting the claim that such chips can emulate human pathophysiology in a more human-like setting. (LLM, conf=0.88)
- Supportedcites [51] Si, L. et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat. Biomed. Eng. 5, 815–829 (2021). source
The Abstract says Organ Chips can recapitulate human organ physiology and disease states, and describes Lung Chips as mimicking human lung responses to infection. The Results section describes an Airway Chip with cell types and barrier properties similar to those of the human airway in vivo, supporting the claim that it provides a more human-like setting. (LLM, conf=0.93)
- Partly supportedcites [55] Maschmeyer, I. et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15, 2688–2699 (2015). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes multi-organ chips as combining organ equivalents in a human-like metabolizing environment. The Conclusions (page unavailable) report sustained physiological tissue architecture and homeostasis in the four-organ chip. The paper does not demonstrate that the chip reproduces pathological states, so the pathophysiology part is not established. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the biomimicry of tissue-specific transporters and cell junctions is often higher in 3D models13.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
What the sources say
- Partly supportedcites [13] DesRochers, T. M., Suter, L., Roth, A. & Kaplan, D. L. Bioengineered 3D human kidney tissue, a platform for the determination of nephrotoxicity. PLoS One 8, e59219 (2013). sourceExperimental — accuracy not yet measured
In ‘Establishment and Characterization of Bioengineered 3D Human Renal Tissue Constructs’ (page unavailable), the paper reports that some kidney transporter transcripts were detected in 3D tissue but not in 2D culture, suggesting a more in vivo-like phenotype. It also reports E-cadherin expression in the 3D tissue, but does not show that cell junctions are better mimicked than in 2D or establish the claim across 3D models generally. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“central pathomechanisms, such as the contribution of endothelial dysfunction, the ‘cytokine storm’ and the intercellular variability of infection susceptibility, were identified in organoids and lung-on-a-chip models82–86.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [82] Lu, R. X. Z. et al. Vasculature-on-a-chip platform with innate immunity enables identification of angiopoietin-1 derived peptide as a therapeutic for SARS-CoV-2 induced inflammation. Lab Chip 22, 1171–1186 (2022). sourceExperimental — accuracy not yet measured
The Results and Discussion report endothelial barrier dysfunction and increased inflammatory cytokines after SARS-CoV-2 exposure, with PBMCs amplifying the response. But this study used a vasculature-on-a-chip, not an organoid or lung-on-a-chip, and it did not establish intercellular variability in infection susceptibility in those models. Page numbers are unavailable in our copy. (LLM, conf=0.87)
- Supportedcites [83] Zhang, M. et al. Biomimetic human disease model of SARS-CoV-2 induced lung injury and immune responses on organ chip system. Adv. Sci. 8, 2002928 (2020). source
The Discussion reports that the alveolus-on-a-chip model showed microvascular endothelial dysfunction and excessive inflammatory responses, including increased cytokine release. The Results and Discussion also report that alveolar epithelial cells were more susceptible to SARS-CoV-2 infection than endothelial cells. The paper studies a lung-on-a-chip model; the citing sentence refers collectively to organoid and chip models across several citations. (LLM, conf=0.90)
- Partly supportedcites [84] Katsura, H. et al. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Cell Stem Cell 27, 890–904.e8 (2020). sourceExperimental — accuracy not yet measured
The Results section reports that SARS-CoV-2-infected alveolospheres activate interferon and inflammatory pathways, supporting the claim that an organoid model revealed a COVID-19-related mechanism. The Introduction mentions a ‘cytokine storm’ as clinical background, but the paper does not show that its model identified a cytokine storm, endothelial dysfunction, or intercellular differences in infection susceptibility. No page numbers are available in our copy. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“iPS cell-derived organoids fail to mature beyond the fetal phenotype unless they are grafted into living organisms36,37.”
§ Human disease models in drug development > Overview of human disease models > Organoids
What the sources say
- Partly supportedcites [36] Mansour, A. A. et al. An in vivo model of functional and vascularized human brain organoids. Nat. Biotechnol. 36, 432–441 (2018). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report more mature-neuron-marker-positive cells in grafted organoids than in nearly stage-matched cultured organoids, suggesting that the in vivo environment enhanced maturation and/or survival. But the paper says cultured organoids also develop mature neurons, and the Discussion (page unavailable) says whether transplantation enhances functional maturation requires further research. Its grafting experiments used hESC-derived, not iPSC-derived, organoids; it does not establish that implantation is necessary to progress beyond a fetal phenotype. (LLM, conf=0.88)
- Partly supportedcites [37] Revah, O. et al. Maturation and circuit integration of transplanted human cortical organoids. Nature 610, 319–326 (2022). sourceExperimental — accuracy not yet measured
The Main section reports that transplanted cortical organoids were more mature than age-matched organoids kept in vitro. But it also says both groups’ overall transcriptomic maturation was most equivalent to the late fetal period. The paper therefore supports improved maturation after grafting, not the claim that grafting is required to move beyond a fetal phenotype. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“3D cultures of lung fibroblasts resemble in vivo tumour necrosis factor (TNF) receptor expression and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation patterns more closely than 2D cultures12.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
What the sources say
- Supportedcites [12] Htwe, S. S. et al. Investigating NF-κB signaling in lung fibroblasts in 2D and 3D culture systems. Respir. Res. 16, 144 (2015). source
The Abstract states that the TNF receptor I expression pattern and NF-κB responses in 3D cultures collectively reflect a more in vivo-like pattern than in 2D cultures. The results sections describe the differing receptor-expression and activation patterns underlying that conclusion. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“base editors yield 61% in vivo gene editing efficacy in the liver of mice compared to 26% in primates8.”
§ Human disease models in drug development > Introduction
What the sources say
- Supportedcites [8] Rothgangl, T. et al. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat. Biotechnol. 39, 949–957 (2021). source
The paper’s Abstract (page not provided) reports average liver-editing rates of 61% in mice and 26% in macaques, matching the cited comparison. These are averages for the PCSK9-targeting adenine base editor used in this study, not editing rates for all base editors. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A vasculature-on-a-chip setup revealed that SARS-CoV-2 exposure substantially reduces endothelial barrier function by perturbing vascular endothelial–cadherin junctions and increasing pro-inflammatory cytokine release.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [82] Lu, R. X. Z. et al. Vasculature-on-a-chip platform with innate immunity enables identification of angiopoietin-1 derived peptide as a therapeutic for SARS-CoV-2 induced inflammation. Lab Chip 22, 1171–1186 (2022). source
The Results section ('SARS-CoV-2 treatment in the InVADE model') reports increased vascular permeability, disrupted VE-cadherin junctions, and significantly increased pro-inflammatory cytokines 72 hours after infection. It also notes that permeability and junctions had not changed at 48 hours. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Animal models, however, often fail to filter out harmful or ineffective drugs6.”
§ Human disease models in drug development > Introduction
What the sources say
- Supportedcites [6] Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467–491 (2022). source
The Introduction says animal-study results often fail to predict human responses and describes drugs that passed animal testing but later proved ineffective or caused potentially life-threatening toxicity in human trials. This supports the claim that animal models often fail to filter out harmful or ineffective drugs. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Most drugs fail in clinical stages (Fig. 1) despite proven efficacy and safety in animal models4,5.”
§ Human disease models in drug development > Introduction
What the sources say
- Could not verifycites [4] Golding, H., Khurana, S. & Zaitseva, M. What is the predictive value of animal models for vaccine efficacy in humans? The importance of bridging studies and species-independent correlates of protection. Cold Spring Harb. Perspect. Biol. 10, a028902 (2018). sourceExperimental — accuracy not yet measured
The Concluding Remarks (page not provided) describe a low success rate in establishing animal models predictive of vaccine effectiveness, not a failure rate for drugs in clinical trials. A search for drug failures after demonstrated animal efficacy and safety found no passage addressing that claim. (LLM, conf=0.76)
- Partly supportedcites [5] Franco, R. & Cedazo-Minguez, A. Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans? Front. Pharmacol. 5, 146 (2014). sourceExperimental — accuracy not yet measured
The Introduction and the section on the gap between mouse models and human patients describe treatments that succeed in Alzheimer’s animal models but yield inconclusive or negative clinical results. The paper does not establish that those treatments had proven safety in animals, and its discussion is specific to Alzheimer’s therapies rather than drugs generally. No page numbers are available in our copy. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“114 PDO cultures from 101 patients were generated127 and subjected to transcriptomic profiling, followed by therapeutic profiling”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Partly supportedcites [127] Tiriac, H. et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 8, 1112–1129 (2018). sourceExperimental — accuracy not yet measured
The Results section, “Assembling a pancreatic cancer patient-derived organoid library” (page unavailable), reports 114 PDO cultures generated from 101 patients. But “Transcriptomic profiling and subtyping” reports RNA sequencing of 44 PDAC-confirmed PDOs, and “PDO pharmacotyping corresponds with individual patient treatment responses” reports therapeutic profiling of 66. The source does not support the implication that all 114 underwent both types of profiling. (LLM, conf=0.92)
plainn = 101- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a screen of small molecules that correct dysregulated gene networks in NOTCH1-deficient calcific aortic valve disease (CAVD) was combined with a machine learning algorithm that was trained to classify gene expression levels as wild type or diseased, allowing the detection of target molecules in patient-derived iPS cells108.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [108] Theodoris, C. V. et al. Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease. Science 371, eabd0724 (2021). source
The Main Text describes a screen for molecules that correct the network dysregulated by NOTCH1 haploinsufficiency in iPSC-derived endothelial cells from a patient with aortic valve stenosis and CAVD. In “Network-based screen identifies network-correcting small molecules,” it says a K-nearest-neighbors algorithm classified gene expression as wild type or NOTCH1-haploinsufficient to support the screen. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“high-throughput screens of ≥1,000 drugs approved by the FDA run on colonic and lung organoids identified several SARS-CoV-2 entry inhibitors such as imatinib, mycophenolic acid and quinacrine dihydrochloride111.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [111] Han, Y. et al. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature 589, 270–275 (2021). sourceExperimental — accuracy not yet measured
The “A hPSC-LOs-based anti-SARS-CoV-2 screen” section identifies imatinib, mycophenolic acid and quinacrine dihydrochloride as entry-inhibitor hits from an FDA-approved drug library. But the high-throughput screen used lung organoids only; colonic organoids were used for subsequent validation (“Drugs block SARS-CoV-2 infection”). Our copy does not give a library size confirming ≥1,000 drugs. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Multi-omics and multiplexed cytokine and chemokine analysis revealed that short-chain fatty acids increase the expression of pathways related to ferroptosis in Parkinson disease models”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [103] Trapecar, M. et al. Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases. Sci. Adv. 7, eabd1707 (2021). source
The Results section reports that SCFA exposure increased pathways associated with ferroptosis in PD microphysiological systems. The Discussion specifies that this increase occurred in PD but not corrected PD systems, alongside analysis of inflammatory cytokines. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Combinations of phenotypic screens with multi-omics technologies can further increase the success in early phases of drug development, especially for diseases with a complex genetic background10.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [10] Brooks, I. R. et al. Functional genomics and the future of iPSCs in disease modeling. Stem Cell Rep. 17, 1033–1047 (2022). source
In “Functional genomics in hiPSC-based drug screening,” the paper describes phenotypic screening and says that functional-genomics screening using multi-omics measurements could improve drug-development success for diseases with a complex genetic component. This supports the cited sentence’s qualified claim about combining these approaches in drug screening. (LLM, conf=0.91)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“an increase in S100A7 expression was observed which codes for alarmins and receptor for advanced glycation end products (RAGE) ligands.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [113] Bai, H. et al. Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nat. Commun. 13, 1928 (2022). sourceExperimental — accuracy not yet measured
In “Mechanical strain increases innate immunity in Lung Chips,” the paper reports significantly higher S100A7 mRNA in strained alveolus chips than in static controls. It also identifies S100A7 as an alarmin-family protein and a RAGE ligand. The paper does not supply a page number for this passage. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“testing of treatment responses in intestinal patient-derived organoids (PDOs) has emerged as a reliable and predictive approach118,119.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Not checked — no full text of the sourcecites [118] Dekkers, J. F. et al. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci. Transl. Med. 8, 344ra384 (2016). source
- Supportedcites [119] Berkers, G. et al. Rectal organoids enable personalized treatment of cystic fibrosis. Cell Rep. 26, 1701–1708.e3 (2019). source
The Summary (p. 3) reports that drug responses in patient-derived rectal organoids correlated with two clinical treatment-response measures and that the test had good-to-excellent accuracy for identifying clinical responses. The Conclusion (p. 8) says the assay can predict individual benefits from CFTR-modulator treatment, supporting the claim in that context. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the brain, alternative receptors, such as CD147 and DPP4, are required for infection and virus replication as shown in astrocytes88.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [88] Andrews, M. G. et al. Tropism of SARS-CoV-2 for human cortical astrocytes. Proc. Natl Acad. Sci. USA 119, e2122236119 (2022). sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says the findings suggest CD147 is necessary and DPP4 is sufficient for SARS-CoV-2 infection in cortical astrocytes. It also says low-level infection can persist when both are inhibited. The citing sentence overstates this as a requirement for both receptors in brain infection and viral replication generally. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“applying physiological breathing mechanics in alveoli-on-chip models showed antiviral activity by increasing the expression of interferon-related genes and improving host defence113.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [113] Bai, H. et al. Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nat. Commun. 13, 1928 (2022). source
The “Mechanical strain increases innate immunity in Lung Chips” section reports that breathing-like deformations increased expression of multiple interferon-related antiviral genes. The “Influenza A virus infection of the human lung alveolus chip” section reports lower viral mRNA and viral titers in mechanically stimulated chips than in static controls, supporting the claimed antiviral effect and improved host defence. Page numbers were not available in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the E. coli strain Nissle 1917, commonly used as a probiotic, also produces colibactin102”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [102] Nougayrède, J. P. et al. A toxic friend: genotoxic and mutagenic activity of the probiotic strain Escherichia coli Nissle 1917. mSphere 6, e0062421 (2021). source
The Results section reports that wild-type Nissle 1917 produced a colibactin cleavage product and concludes that it synthesizes mature colibactin. The Discussion identifies Nissle 1917 as a probiotic. Page numbers are not provided in the supplied passages. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This connection has been confirmed using an OoC setup that emulates the immune–metabolic crosstalk between these tissues103.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [103] Trapecar, M. et al. Human physiomimetic model integrating microphysiological systems of the gut, liver, and brain for studies of neurodegenerative diseases. Sci. Adv. 7, eabd1707 (2021). sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that the gut–liver–brain physiomimetic system, with immune cells and short-chain fatty acids, produced stronger Parkinson’s-associated gene-expression changes in the Parkinson’s model. The Discussion (page unavailable) says the system recreates only a subset of disease hallmarks, so the experiment supports a possible connection rather than confirming the gut–liver–brain axis’s role in Parkinson’s disease generally. (LLM, conf=0.84)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The treatment outcome of the PDOs positively correlated with individual patient responses”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Supportedcites [127] Tiriac, H. et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 8, 1112–1129 (2018). source
In Results, under “PDO pharmacotyping corresponds with individual patient treatment responses,” matched PDO drug sensitivity generally aligned with outcomes in nine patients with advanced pancreatic cancer: five of six patients with longer progression-free survival received a drug to which their PDO was sensitive, while two of three who progressed rapidly received a drug to which their PDO was resistant. The paper notes one inconsistent case, so the finding is a general correspondence rather than a perfect match. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“revealing strong correlations between in vitro and in vivo drug responses against cancer in the gastrointestinal tract123, bladder124, ovary125, rectum126 and pancreas127,128.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Not checked — no full text of the sourcecites [123] Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018). source
- Partly supportedcites [124] Lee, S. H. et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173, 515–528.e17 (2018). sourceExperimental — accuracy not yet measured
In “Drug Response of Organoid Lines” (32 e11–16), three bladder-organoid drug responses observed in culture were also observed in orthotopic xenografts in vivo. This supports agreement for those tested combinations, but not a general claim of strong correlations across bladder-cancer drug responses. The Discussion says studies comparing organoid responses with patients’ responses remain a next step. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [125] Hill, S. J. et al. Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids. Cancer Discov. 8, 1404–1421 (2018). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“An OoC-based chronic inflammatory demyelinating polyneuropathy electrical conduction model, consisting of human iPS cell-derived motor neurons and Schwann cells cultivated on microelectrode arrays, closely emulates clinically relevant features such as muscle contraction and electrical activity.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [116] Rumsey, J. W. et al. Classical complement pathway inhibition in a “human-on-a-chip” model of autoimmune demyelinating neuropathies. Adv. Ther. 5, 2200030 (2022). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes a CIDP human-on-a-chip model with iPSC-derived motor neurons and human Schwann cells cultured on microelectrode arrays. The Results (page unavailable) report measurements of electrical activity and conduction velocity, but the paper does not report that the model reproduces muscle contraction. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“among eight drugs with dose-dependent inhibition of virus uptake in static Huh-7 cell monolayers, only three (amodiaquine, toremifene and clomiphene) proved effective in 3D OoC cultures51.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [51] Si, L. et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat. Biomed. Eng. 5, 815–829 (2021). source
The Results section (‘Identification of approved drugs as SARS-CoV-2 entry inhibitors’) says all eight drugs dose-dependently inhibited SARS-CoV-2 pseudovirus entry in Huh-7 cells. In the human Airway Chips, only amodiaquine, toremifene and clomiphene significantly reduced viral entry. The chip result concerns pseudovirus entry at clinically relevant drug concentrations, rather than effectiveness against infection generally. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The RAGE inhibitor azeliragon was then identified as effective by suppressing the overshooting of inflammatory responses as observed in patients who were severely ill with COVID-19.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [113] Bai, H. et al. Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nat. Commun. 13, 1928 (2022). sourceExperimental — accuracy not yet measured
The “RAGE inhibitors suppress viral infection-induced inflammatory responses” section and Fig. 8 report that azeliragon reduced inflammatory cytokine secretion in human alveolus chips infected with H3N2 influenza virus. The Discussion relates this response to severe COVID-19 and proposes azeliragon as a treatment option, but the paper does not show that azeliragon was effective in patients with severe COVID-19. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Single-cell and spatial profiling at transcriptional, proteomic and epigenetic levels (Box 2) can substantially improve disease model validation161,162”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Partly supportedcites [161] Li, X. & Wang, C.-Y. From bulk, single-cell to spatial RNA sequencing. Int. J. Oral. Sci. 13, 36 (2021). sourceExperimental — accuracy not yet measured
The Concluding Remarks (page unavailable) say that combining single-cell epigenome, transcriptome and proteome data could profoundly improve understanding of how cancer develops. The paper does not say that this profiling improves disease model validation; searches for disease-model validation and model fidelity found no such passage. (LLM, conf=0.83)
- Partly supportedcites [162] Kip, A. M. et al. Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury. Cell Death Dis. 12, 95 (2021). sourceExperimental — accuracy not yet measured
The Results (page unavailable) use quantitative proteomics to characterize intestinal organoids and their response to hypoxia–reoxygenation, supporting the proteomic aspect of assessing a disease model. The passages do not establish that single-cell or spatial profiling, or transcriptional and epigenetic profiling, improves model validation. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The complex architecture of disease models, their characterization and the investigation of cell-specific pathological reactions require advanced 3D imaging technologies, such as light-sheet fluorescence microscopy or multiphoton imaging167”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Partly supportedcites [167] Fei, K., Zhang, J., Yuan, J. & Xiao, P. Present application and perspectives of organoid imaging technology. Bioengineering 9, 121 (2022). sourceExperimental — accuracy not yet measured
The Discussion (section 3; page unavailable) says organoids’ complex 3D structure demands imaging that resolves both whole structures and cellular-level features, and identifies light-sheet and two-photon microscopy as 3D imaging options. Section 2.3 says intravital multiphoton microscopy permits single-cell observation of pathology. The paper supports this point for organoids and a specific multiphoton application, but does not establish that these technologies are required for disease models generally. (LLM, conf=0.79)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These considerations ensure the correct translation of the key functional indices from the model to in vivo conditions139”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Partly supportedcites [139] Maass, C., Stokes, C. L., Griffith, L. G. & Cirit, M. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integr. Biol. 9, 290–302 (2017). sourceExperimental — accuracy not yet measured
The Introduction describes functional scaling as a way to recapitulate selected in vivo functions, and the Results and Discussion report that multi-functional scaling captured drug-exposure times similar to those in vivo. But the paper does not say these considerations ensure correct translation of functional indices generally; it cautions that translation depends on adequately capturing in vivo physiology. The provided passages have section labels but no page numbers. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Unlike 2D imaging, these technologies allow high-resolution 3D whole-mount imaging of disease models at different scales, including cellular compositions, cell shapes, cell–cell interactions and cell fate167”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Supportedcites [167] Fei, K., Zhang, J., Yuan, J. & Xiao, P. Present application and perspectives of organoid imaging technology. Bioengineering 9, 121 (2022). source
The Introduction says that, unlike 2D imaging, 3D methods characterize whole-mount tissue from cell to tissue scale and help reveal cellular composition, cell shape, cell–cell interactions and cell fate. The Discussion describes organoids as biological models requiring whole-object 3D imaging with cellular-level detail, and identifies their use as disease models. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the huge amount of data generated, especially for high-throughput screenings of PDOs, has called for an increasing use of artificial intelligence-driven data analysis algorithms such as machine learning169”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Partly supportedcites [169] Busek, M., Aizenshtadt, A., Amirola-Martinez, M., Delon, L. & Krauss, S. Academic user view: organ-on-a-chip technology. Biosensors 12, 126 (2022). sourceExperimental — accuracy not yet measured
The Overview of Organ-on-Chip Technology (p. 4) says that high-throughput screening and advanced readout methods generate large amounts of data, creating an increasing need for machine learning in data analysis. It makes this point about organ-on-a-chip technology generally, not specifically about high-throughput screening of patient-derived organoids (PDOs). (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Tissue geometry and curvature influence cell behaviour, tissue formation and function, and therefore the (patho)physiological relevance of in vitro models181”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Partly supportedcites [181] Werner, M. et al. Surface curvature differentially regulates stem cell migration and differentiation via altered attachment morphology and nuclear deformation. Adv. Sci. 4, 1600347 (2017). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) describes effects of curvature on cell behaviour and tissue growth, and the Conclusions report curvature-dependent stem-cell migration and differentiation. The paper does not establish the further claim that these effects determine the (patho)physiological relevance of in vitro models. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Its importance has been recognized early on, but a general principle is still lacking132–134”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Not checked — no full text of the sourcecites [132] Ronaldson-Bouchard, K. & Vunjak-Novakovic, G. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell 22, 310–324 (2018). source
- Not checked — no full text of the sourcecites [133] Park, D., Lee, J., Chung, J. J., Jung, Y. & Kim, S. H. Integrating organs-on-chips: multiplexing, scaling, vascularization, and innervation. Trends Biotechnol. 38, 99–112 (2020). source
- Supportedcites [134] Malik, M., Yang, Y., Fathi, P., Mahler, G. J. & Esch, M. B. Critical considerations for the design of multi-organ microphysiological systems (MPS). Front. Cell Dev. Biol. 9, 721338 (2021). source
The Introduction (page unavailable) describes establishing globally uniform, reproducible design criteria for multi-organ MPS as an opportunity, and the Conclusion says variability in these systems creates a need for standardization. The paper offers scaling guidance, but its discussion supports the narrower point that a generally established approach is still lacking for these models. (LLM, conf=0.83)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Biomechanical stimuli, such as shear stress, stretching or compression, influence (patho)physiological processes142–147”
§ Human disease models in drug development > Framework for disease model design > Biomechanical cues
What the sources say
- Supportedcites [142] Frye, M. et al. Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat. Commun. 9, 1511 (2018). source
The Discussion states that mechanical forces including shear, stretching and compression regulate cell behavior and fate during development, homeostasis and disease. This supports the citing sentence’s broad claim about their influence on (patho)physiological processes. (LLM, conf=0.94)
- Partly supportedcites [143] Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010). sourceExperimental — accuracy not yet measured
The Reconstitution of a Functional Alveolar-Capillary Interface section (page unavailable) reports physiological effects of cyclic stretching, and the nanoparticle-response section reports that breathing-related strain may accentuate lung inflammation. The paper also reports a modest effect of shear stress on nanoparticle transport, but the passages do not establish an effect of compression; the claim is broader than this lung-chip evidence. (LLM, conf=0.84)
- Partly supportedcites [144] Sontheimer-Phelps, A. et al. Human colon-on-a-chip enables continuous in vitro analysis of colon mucus layer accumulation and physiology. Cell Mol. Gastroenterol. Hepatol. 9, 507–526 (2020). sourceExperimental — accuracy not yet measured
The Results section (page unavailable) reports that flow-induced shear stress bent the colonic mucus layer, which is part of the intestinal barrier. It does not show that this response altered a physiological or pathological process, or that stretching or compression did so; the mention of compression concerns a tissue-fixation artifact. (LLM, conf=0.83)
- Partly supportedcites [145] Bein, A. et al. Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip. Front. Pharmacol. 12, 718484 (2021). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says fluid flow and cyclic peristalsis-like mechanical deformations affect cell differentiation and function relevant to physiology and pathophysiology. This supports the general point and examples akin to shear stress and stretching, but our copy does not establish the stated effect for compression. (LLM, conf=0.83)
- Partly supportedcites [146] Huh, D. et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4, 159ra147 (2012). sourceExperimental — accuracy not yet measured
The Results section, “Pathological changes in barrier integrity” (page unavailable), shows that cyclic stretching during IL-2 exposure increased lung-barrier permeability and contributed to pulmonary edema. This supports stretching as an example of a biomechanical stimulus influencing a pathological process, but the cited paper does not establish the corresponding effects of shear stress or compression. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [147] Grassart, A. et al. Bioengineered human organ-on-chip reveals intestinal microenvironment and mechanical forces impacting shigella infection. Cell Host Microbe 26, 435–444.e4 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“there are sex-related differences in how men and women absorb, distribute and metabolize drugs, ultimately affecting drug efficacy and safety48,130,131.”
§ Human disease models in drug development > Preclinical and clinical applications > Future applications in clinical trials
What the sources say
- Partly supportedcites [48] Lock, R. et al. A framework for developing sex-specific engineered heart models. Nat. Rev. Mater. 7, 295–313 (2021). sourceExperimental — accuracy not yet measured
The “Drug efficacy and toxicity” subsection (page unavailable) reports sex differences in drug efficacy, adverse reactions, and the metabolism of cardiovascular drugs. It does not specifically establish sex differences in drug absorption or distribution, so those parts of the attributed claim are unsupported. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [130] Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626–638 (2016). source
- Not checked — no full text of the sourcecites [131] Zeng, Z. et al. Sex-hormone-driven innate antibodies protect females and infants against EPEC infection. Nat. Immunol. 19, 1100–1111 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a survey amongst scientists that do not use OoC setups revealed that the lack of ready-to-use-systems and production facilities as well as high entry barriers and costs are the main reasons for not employing OoCs169”
§ Human disease models in drug development > Outlook
What the sources say
- Supportedcites [169] Busek, M., Aizenshtadt, A., Amirola-Martinez, M., Delon, L. & Krauss, S. Academic user view: organ-on-a-chip technology. Biosensors 12, 126 (2022). source
Section 3.2 (p. 5) reports that surveyed researchers not using OoC platforms cited unavailable ready-to-use devices and production facilities, complicated use (a high entry barrier), and high costs as concerns. The citing sentence accurately summarizes those reported obstacles. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Out of these, 10 studies are already using PDOs for clinical decision-making (Table 1).”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No results were retrieved for the search term ‘organ-on-chip’ or ‘microphysiological system’.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, their high target specificity requires the identification of cross-reactive species during preclinical testing.”
§ Human disease models in drug development > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Inter-tissue crosstalk and complex in vivo-like processes cannot be mimicked in single and static tissue models.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, drug safety or efficacy issues that only affect certain subpopulations go unnoticed.”
§ Human disease models in drug development > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Species-specificity is also a concern for gene therapies because genetic sequences and therapeutic efficacy differ between animals.”
§ Human disease models in drug development > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In addition, animals are inbred and kept under standardized conditions and thus do not account for the genetic and ethnic diversity of humans.”
§ Human disease models in drug development > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the epithelial differentiation stages of stratified epithelia, such as the skin, cannot be mimicked in 2D.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the drug attrition rate hit an all-time high of 95% in 2021 (ref. 3).”
§ Human disease models in drug development > Introduction
What the sources say
- Not matchedcites [3] IQVIA Institute. Global Trends in R&D 2022 (IQVIA Institute, 2021).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“they are still complex and thereby not amenable to high-throughput methods.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Eventually, enterocytes were identified as the primary target for viral infection”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [96] Ettayebi, K. et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 353, 1387–1393 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“These screens, which are typically conducted in genetically engineered cell lines that harbour the target of interest, led to the discovery of the splice modulators risdiplam106 and branaplam107 for the treatment of spinal muscular atrophy”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [106] Naryshkin, N. A. et al. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 345, 688–693 (2014). source
- Not checked — no full text of the sourcecites [107] Palacino, J. et al. SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice. Nat. Chem. Biol. 11, 511–517 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the expression levels of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in brain organoids are substantially lower than in the lung or intestinal epithelium.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“co-cultivation of liver, gut, and a mixture of neurons, astrocytes and microglia facilitated the maturation of the brain model”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a living biobank of cancer PDOs from patients with metastatic and pre-treated colorectal and gastroesophageal cancer shows strong morphological, genotypic and spatiotemporal similarities between the primary tumour and the PDOs123.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Not checked — no full text of the sourcecites [123] Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“MCLA-158, a bispecific antibody binding epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), was identified as the most effective antibody against wild-type and KRAS-mutant CRC after screening a large biobank of patient-derived CRC organoids.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [114] Herpers, B. et al. Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat. Cancer 3, 418–436 (2022). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“genotoxic E. coli strains were found to cause single base substitutions and indel formations in the intestinal epithelium and other tissues such as the urinary tract.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [101] Pleguezuelos-Manzano, C. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269–273 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the efficacy of amivantamab, a bispecific antibody against EGFR and the mesenchymal–epithelial transition receptor, was preclinically tested in patient-derived cells and organoids that harbour EGFR Exon20ins mutations115.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [115] Yun, J. et al. Antitumor activity of Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in diverse models of EGFR exon 20 insertion-driven NSCLC. Cancer Discov. 10, 1194–1209 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Since 2011, five approved first-in-class drugs for neurodegenerative diseases were identified through phenotypic screening of 2D cultures105.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [105] Swalley, S. E. Expanding therapeutic opportunities for neurodegenerative diseases: a perspective on the important role of phenotypic screening. Bioorg Med. Chem. 28, 115239 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“PDOs reliably predicted treatment responses in patients, with 100% sensitivity, 93% specificity, 88% positive predictive value and 100% negative predictive value, including response to taxanes and anti-EGFR antibodies”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Not checked — no full text of the sourcecites [123] Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies demonstrate that implementing PDOs in clinical decision-making can directly benefit patients with cancer.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Importantly, MCLA-158 reliably discriminated between cancerous and healthy cells.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [114] Herpers, B. et al. Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat. Cancer 3, 418–436 (2022). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Rodent models cannot fully reproduce the mechanism by which the virus causes microcephaly because the human brain has an additional cortical layer containing radial glial cells (progenitor cells).”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The human brain has an additional cortical layer containing radial glial progenitor cells.
In the paper
“infecting intestinal organoids with strains of Escherichia coli that produce the genotoxin colibactin revealed mutation signatures that could drive colorectal cancer (CRC) progression, similar to those found in human tumours101.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [101] Pleguezuelos-Manzano, C. et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature 580, 269–273 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A true scientific leap was the establishment of an in vitro cultivation method for human norovirus in 2016 (ref. 96).”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [96] Ettayebi, K. et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 353, 1387–1393 (2016). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, protocols for cell differentiation into disease models can span several weeks, especially for multicellular tissue models”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These features cannot be recapitulated 1:1 in vitro because it is difficult to control the formation, dimensions and shapes of tissue-relevant geometric structures, which often results in high model variability and limited biomimicry”
§ Human disease models in drug development > Framework for disease model design > Model scaling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, even such a long lifespan might not be sufficient to study neural diseases that develop or progress slowly — for example, Alzheimer disease and Parkinson disease”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For an OoC, this matching could consist of proper ratios of the geometric lengths, morphologically correct arrangement of the cell types, and suitable ratios of mechanical and metabolic rates”
§ Human disease models in drug development > Framework for disease model design > Model scaling
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This strategy could substantially expedite the generation of multicellular disease models”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The establishment and expansion of PDOs and subsequent drug testing currently span several weeks or even months”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, dynamic, time-dependent operating conditions are more difficult to scale”
§ Human disease models in drug development > Framework for disease model design > Model scaling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Another limiting factor is the complexity of data analysis of single-cell proteomics, which has limited the routine application of this technology for model validation so far”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as is identifying a universal culture medium that can maintain tissues of different germ layers in multi-organ models”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even static 3D tissue models are substantially more expensive and technically demanding than conventional 2D biomedical methods”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Scaling an in vitro disease model with an in vivo organ boils down to matching the dimensionless groups between the two”
§ Human disease models in drug development > Framework for disease model design > Model scaling
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These examples highlight the importance of applying disease-relevant and tissue-relevant biomechanical cues in bioengineered models”
§ Human disease models in drug development > Framework for disease model design > Biomechanical cues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A sequential and physiological exposure to biomechanical cues promotes the differentiation and maturation of organoids and bioengineered tissue models”
§ Human disease models in drug development > Framework for disease model design > Biomechanical cues
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using omics technologies, differences in gene regulation and signalling pathways between organoids and the corresponding primary tissue samples can be identified”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Generating tissue-specific niches by introducing native endothelial barriers in OoC setups might hold a solution for this problem; while these barriers keep the tissue models in their optimized environment by separating them from a common media circuit, inter-tissue communication is still possible through the exchange of, for example, cytokines or exosomes150”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Not checked — no full text of the sourcecites [150] Ronaldson-Bouchard, K. et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat. Biomed. Eng. 6, 351–371 (2022). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The limited regenerative capacity of primary cell-based models is a major limitation”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Failing to integrate them would ultimately limit the predictive value of disease models”
§ Human disease models in drug development > Framework for disease model design > Cell diversity and tissue biomimicry
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the overexpression of transcription factors relevant to the differentiation of the target tissue (for example, ETV2 for endothelial cells or NGN1 for neurons) can switch on rapid cell differentiation”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Subsequent mixing or controlled spatial patterning through, for example, 3D printing of iPS cells pre-programmed for doxycycline-induced overexpression of such cell type-specific transcription factors, ultimately facilitates the differentiation into multicellular and spatially patterned organoids independently from extracellular differentiation cues present in the culture medium153”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Not checked — no full text of the sourcecites [153] Skylar-Scott, M. A. et al. Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues. Nat. Biomed. Eng. 6, 449–462 (2022). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the notion that in vitro methods are cheaper is misleading because bioengineered disease models can be as if not more expensive than animal models”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This consideration directly feeds into the choice of model type as not all of them allow the integration of physical forces per se”
§ Human disease models in drug development > Framework for disease model design > Biomechanical cues
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Emulating the fine-tuned and highly interdependent immunoregulation in the human body remains a main limitation of in vitro human disease models”
§ Human disease models in drug development > Challenges and limitations > Immunoregulation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this case, the simplicity of bioengineered human disease models could prove advantageous because disease-relevant effects might appear more rapidly owing to the lack of compensatory mechanisms that typically exist in vivo that can compensate for or mask tissue dysfunction”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Proteomics can thus help unravel disease mechanisms and tissue responses to certain stimuli”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The identification of disease-relevant and tissue-relevant cell types is crucial”
§ Human disease models in drug development > Framework for disease model design > Cell diversity and tissue biomimicry
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the most realistic short-term and mid-term scenario is the complementary use of both human-based and animal models”
§ Human disease models in drug development > Outlook
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as of now, only few disease models are commercially available”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“all commercially available OoC setups are run with pre-set chips, which determines a priori the type and dimension of tissues that can be integrated”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- It may state two separate claims as one. 64
- Probably not a substantial claim. 20
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Non-human primates are often the only pharmacologically relevant species, whose use has ethical and economic implications7.”
§ Human disease models in drug development > Introduction
What the sources say
- Partly supportedcites [7] Brennan, F. R. et al. Safety testing of monoclonal antibodies in non-human primates: case studies highlighting their impact on human risk assessment. mAbs 10, 1–17 (2018). sourceExperimental — accuracy not yet measured
The Discussion (page not specified) says that, for many monoclonal antibodies, non-human primates are the only pharmacologically relevant species. The Introduction calls for ethically justified use and reduced NHP use, but the passages do not address economic implications. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Promising disease models of the liver65,66, pancreas67,68, central nervous system35,69,70, skin71, lung72,73, intestine72–76, musculoskeletal system77 and heart78–81 have been developed, but their equivalence or superiority over their animal models needs to be demonstrated.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [65] Nawroth, J. C. et al. Modeling alcohol-associated liver disease in a human liver-chip. Cell Rep. 36, 109393 (2021). source
The citation is attached to the liver-model example, not to the sentence’s later assessment of equivalence to animal models. The Results section (‘Development of the Liver-Chip for modeling ALD/ASH’) describes a human Liver-Chip built to model alcohol-associated liver disease. (LLM, conf=0.93)
- Partly supportedcites [67] Bauer, S. et al. Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci. Rep. 7, 14620 (2017). sourceExperimental — accuracy not yet measured
The Discussion describes a developed human pancreatic-islet–liver chip that models glucose regulation, supporting its citation as a promising pancreatic platform. But it says inducing type 2 diabetes conditions is a next step; the paper does not establish that this chip already models the disease. The source does not compare its performance with animal models. (LLM, conf=0.86)
- Supportedcites [35] Lancaster, M. A. et al. Cerebral organoids model human brain development and microcephaly. Nature 501, 373–379 (2013). source
The Results section (‘Cerebral organoids model human microcephaly’) describes testing cerebral organoids as a model of a neurodevelopmental disorder. This supports citing the paper as an example of a central nervous system disease model; the other organ systems are covered by other citations in the sentence. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“most animal models poorly resemble human conditions and thus have low predictive values.”
§ Human disease models in drug development > Introduction
What the sources say
- Partly supportedcites [6] Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467–491 (2022). sourceExperimental — accuracy not yet measured
The Introduction says animal-study results often fail to predict human results and that animal disease models can have molecular and cellular mechanisms distinct from those in humans. It does not establish that most animal models poorly resemble human conditions; it notes that some may appear phenotypically similar. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“OoCs are perfused microfluidic platforms that contain bioengineered or miniaturized tissues or organs interconnected by 3D microchannels to simulate the in vivo functions, biomechanics and (patho)physiological responses of organs6,52–54.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
What the sources say
- Partly supportedcites [6] Ingber, D. E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 23, 467–491 (2022). sourceExperimental — accuracy not yet measured
The Introduction describes organ chips as microfluidic devices with living cells and tissues in channels under dynamic fluid flow, designed to model organ functions and disease states. But it says only some recreate mechanical cues, while the Microfluidic organ chips section includes single-channel devices; interconnected tissues and 3D channels are therefore not defining features of all organ chips. The supplied passages have no page numbers. (LLM, conf=0.84)
- Could not verifycites [52] Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug Discov. 20, 345–361 (2021). sourceExperimental — accuracy not yet measured
The passages available from our copy are bibliographic metadata, not a description of how organs-on-chips are constructed or what they simulate. Searches for microfluidic devices, 3D microchannels, biomechanics, and pathophysiological responses found no passage addressing the claim. (LLM, conf=0.74)
- Partly supportedcites [53] Vunjak-Novakovic, G., Ronaldson-Bouchard, K. & Radisic, M. Organs-on-a-chip models for biological research. Cell 184, 4597–4611 (2021). sourceExperimental — accuracy not yet measured
The Introduction describes organs-on-chips as engineered tissue constructs that reproduce selected organ functions using physical signals and fabricated channels. But it says these constructs are not mini-organs, and the section on combining single-organ models describes several ways to connect them—not necessarily 3D microchannels. The claim therefore overstates what all organs-on-chips contain. Page numbers are unavailable in our copy. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“human-based models have so far been primarily used for toxicity testing61–64, and their application in preclinical and clinical research is still in its infancy.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [61] Marx, U. et al. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. Altex 33, 272–321 (2016). sourceExperimental — accuracy not yet measured
Section 5.5 describes chemical safety testing as a major driver of human-based alternative methods. Section 3.1 presents wider pharmaceutical adoption of microphysiological systems, including use during clinical development, as prospective. The paper does not establish that human-based models have been used primarily for toxicity testing or that preclinical and clinical research applications as a whole remain in their infancy; it also describes existing disease-modeling and drug-development applications. Page numbers were not available in our copy. (LLM, conf=0.82)
- Partly supportedcites [62] Matsui, T. & Shinozawa, T. Human organoids for predictive toxicology research and drug development. Front. Genet. 12, 767621 (2021). sourceExperimental — accuracy not yet measured
The Introduction describes toxicity assays using human cells, and the Concluding Remarks discuss human organoids as potential tools for toxicity evaluation. Neither section establishes that human-based models have been used primarily for toxicity testing; the review also says reports of organoid toxicity studies remain very limited. It does not assess whether their preclinical or clinical use is still in its infancy. (LLM, conf=0.77)
- Supportedcites [63] Li, M. et al. Advanced human developmental toxicity and teratogenicity assessment using human organoid models. Ecotoxicol. Environ. Saf. 235, 113429 (2022). source
The Introduction describes a strong shift in human stem-cell applications toward toxicology assessment, and §4 describes organoid use in toxicity screening. These passages support the toxicity-testing clause to which the citation is attached; the preclinical and clinical clause follows the citation. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Biomedical research is undergoing a paradigm shift towards approaches centred on human disease models owing to the notoriously high failure rates of the current drug development process.”
- Also stated in: § Introduction · plain
“Biomedical research is currently undergoing a paradigm shift towards approaches centred on human disease models1. This shift has been driven by the notoriously high failure rates of the current drug development process.”
§ Human disease models in drug development > Abstract
What the sources say
- Partly supportedcites [1] Adhikary, P. P., Ul Ain, Q., Hocke, A. C. & Hedtrich, S. COVID-19 highlights the model dilemma in biomedical research. Nat. Rev. Mater. 6, 374–376 (2021). sourceExperimental — accuracy not yet measured
The Abstract links poorly predictive animal models to high clinical-trial failure rates and says researchers are calling for a shift toward human-centred approaches. It does not establish that biomedical research is already undergoing that shift; the section on available preclinical models says the impact of human-based models remains low. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Introduction · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Multipotent adult stem cells (ASCs) and induced pluripotent stem (iPS) cells can help overcome this shortage, as they can readily and indefinitely propagate and convert into any somatic cell10.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
What the sources say
- Partly supportedcites [10] Brooks, I. R. et al. Functional genomics and the future of iPSCs in disease modeling. Stem Cell Rep. 17, 1033–1047 (2022). sourceExperimental — accuracy not yet measured
The Introduction says primary patient cells are scarce because they proliferate poorly, and describes hiPSCs as having high proliferative capacity and the potential to yield multiple cell types. It does not extend those properties to adult stem cells or say that either cell type propagates indefinitely or can become any somatic cell type. No page numbers are provided in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“biophysical processes, such as chip perfusion, can be easily automated using OoCs, which allows monitoring of tissue function and responses in situ and in real time52.”
§ Human disease models in drug development > Overview of human disease models > Organs-on-chips
What the sources say
- Could not verifycites [52] Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P. & Tagle, D. A. Organs-on-chips: into the next decade. Nat. Rev. Drug Discov. 20, 345–361 (2021). sourceExperimental — accuracy not yet measured
The supplied passages contain bibliographic metadata, not discussion of organ-on-chip capabilities. Searches of our copy for automated chip perfusion and real-time, in situ monitoring of tissue function returned no substantive passage, so the claim cannot be assessed from the available text. (LLM, conf=0.70)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The size of these organ-like structures ranges from 100 µm (lung organoid) to 2 mm (brain organoid) and they can be cultivated in small dimensions (for example, 96-well or 384-well plates25,26), thereby being suitable for high-throughput screening.”
§ Human disease models in drug development > Overview of human disease models > Organoids
What the sources say
- Supportedcites [25] Du, Y. et al. Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening. J. Mol. Cell Biol. 12, 630–643 (2020). source
The citation is attached to the claim about cultivation in 96- or 384-well plates, not the lung and brain size figures. The Introduction describes organoid testing in 96-well plates, and the Results demonstrate human colon organoid culture in 384-well plates with readouts suitable for high-throughput screening. (LLM, conf=0.91)
- Partly supportedcites [26] Vonk, A. M. et al. Protocol for application, standardization and validation of the forskolin-induced swelling assay in cystic fibrosis human colon organoids. STAR Protoc. 1, 100019 (2020). sourceExperimental — accuracy not yet measured
The Forskolin Induced Swelling (FIS) Assay methods describe seeding human colon organoids in 96-well plates, supporting the small-well part of the claim. They do not give the stated 100 µm lung-to-2 mm brain size range or describe cultivation in 384-well plates, and the protocol does not establish high-throughput screening across organoid types. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“At the beginning of the pandemic, it was unclear which species were susceptible to SARS-CoV-2 and no model was readily available to study the course of the disease and identify druggable targets against the unknown pathogen9.”
§ Human disease models in drug development > Introduction
What the sources say
- Partly supportedcites [9] Muñoz-Fontela, C. et al. Animal models for COVID-19. Nature 586, 509–515 (2020). sourceExperimental — accuracy not yet measured
The Abstract says the WHO convened experts in February 2020 to develop COVID-19 animal models, and the Conclusions describe efforts to determine which species are susceptible. These passages support the early uncertainty and need for models, but they do not establish that models were needed specifically to identify druggable targets. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“cell responses and gene and/or protein expression patterns greatly differ between 2D and three-dimensional (3D) models11.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
What the sources say
- Supportedcites [11] Jensen, C. & Teng, Y. Is it time to start transitioning from 2D to 3D cell culture? Front. Mol. Biosci. 7, 33 (2020). source
The Background comparison table says gene and protein expression levels differ markedly between 2D cultures and in vivo-like 3D cultures. The Tumor Models and Immunotherapy section reports large gene-expression discrepancies between 2D and 3D cultures, while 3D Cell Culture for Drug Discovery reports different cellular responses to drugs. These passages support the citing sentence; page numbers are not provided in our copy. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“single-cell RNA sequencing (scRNA-seq) of kidney organoids showed that SARS-CoV-2 directly infects kidney cells, triggering pro-fibrotic events and features of polycystic kidney disease, closely resembling renal processes observed in individuals who are critically ill with COVID-19 (refs. 89,90).”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [89] Jansen, J. et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 29, 217–231.e8 (2022). sourceExperimental — accuracy not yet measured
The Results and discussion sections on kidney organoids report scRNA-seq evidence of infection and profibrotic signaling; the patient-tissue results also report infection and increased fibrosis in COVID-19 kidneys. Our copy does not report polycystic kidney disease features in the organoids or in critically ill patients, so that part of the claimed resemblance is unsupported (pages not provided). (LLM, conf=0.88)
- Partly supportedcites [90] Helms, L. et al. Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations. JCI Insight 6, e154882 (2021). sourceExperimental — accuracy not yet measured
The Results section, ‘SARS-CoV-2 infects organoid proximal tubules with pathogenic effects,’ supports direct infection of kidney organoid cells. But the paper used pre-existing PKD2–/– cystic organoids to test infection; it does not show that infection caused polycystic kidney disease features. The Methods describe using previously available organoid scRNA-seq data, while the patient comparison in Results concerns urinary proteins and interferon-response signatures—not scRNA-seq evidence of pro-fibrotic changes resembling renal processes in critically ill patients. Page numbers were not available in our copy. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“cyclin-dependent kinase inhibitors 4 and 6 (CDK4/6) facilitate T cell activation, resulting in a higher number of tumour-infiltrating T cells in PDOs, cultivated over several days in a microfluidic 3D chip setup.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Partly supportedcites [129] Deng, J. et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 8, 216–233 (2018). sourceExperimental — accuracy not yet measured
The Results section reports that CDK4/6 inhibitors increased cytokines associated with T-cell responses in patient-derived tumor spheroids cultured in 3D microfluidic devices. The Introduction places the increase in tumor-infiltrating T cells in vivo, not in those spheroids. The cited paper therefore supports T-cell activation and the chip model, but not the claimed higher number of infiltrating T cells in that model. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Almost 1,600 molecules were screened using targeted RNA sequencing, resulting in the identification of an inverse agonist of oestrogen-related receptor-α as the lead compound, which proved effective in correcting dysregulated CAVD-relevant genes in primary aortic valve endothelial cells from individuals with CAVD and in genetically modified mice.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [108] Theodoris, C. V. et al. Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease. Science 371, eabd0724 (2021). source
The Discussion reports targeted RNA-seq screening of nearly 1,600 small molecules and identifies XCT790 as the most effective network-correcting molecule. It calls XCT790 an ERRα inverse agonist and reports correction of dysregulated genes in primary valve endothelial cells from patients with CAVD. The in vivo results report correction of dysregulated genes in the genetically modified mouse model. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“amodiaquine (for example, NCT04532931, NCT04502342)51 and imatinib111 (for example, NCT04394416) have entered clinical trials.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [51] Si, L. et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat. Biomed. Eng. 5, 815–829 (2021). source
The Discussion states that human Phase 2 COVID-19 treatment trials using amodiaquine had recently begun in Africa. Citation 51 is attached to amodiaquine; the sentence cites a different source for imatinib, so imatinib is not assessed here. (LLM, conf=0.93)
- Could not verifycites [111] Han, Y. et al. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature 589, 270–275 (2021). sourceExperimental — accuracy not yet measured
The citation to this paper is attached to imatinib, not amodiaquine. The ‘Drugs block SARS-CoV-2 infection’ section reports imatinib experiments in organoids and Vero cells, but our copy does not say that imatinib entered a clinical trial or mention NCT04394416 (searched: clinical trials and the trial identifier). (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SARS-CoV-2 tropism for neurons87 and cortical astrocytes88 or its preference for mature cell types and distinct neurotoxic effects were demonstrated in brain organoids.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [87] Ramani, A. et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 39, e106230 (2020). source
The Results section reports SARS-CoV-2 entry into neurons of brain organoids and more virus-positive cells in Day-60 than Day-15 organoids, suggesting a preference for relatively mature neuronal cells. It also reports altered Tau localization and increased neuronal cell death after exposure. The citing sentence attaches the cortical-astrocyte claim to a different citation (88), so that claim is not assessed against this paper. (LLM, conf=0.91)
- Partly supportedcites [88] Andrews, M. G. et al. Tropism of SARS-CoV-2 for human cortical astrocytes. Proc. Natl Acad. Sci. USA 119, e2122236119 (2022). sourceExperimental — accuracy not yet measured
The Results section on gliogenic cortical organoids (page unavailable) reports robust infection of astrocytes in week-22 organoids, but only rare infection of neurons. The paper supports astrocyte tropism and greater infection at a later organoid stage; it does not establish a general preference for mature cell types. The neuron-tropism claim is attached to citation 87, not this source, and the supplied organoid results do not establish the claimed distinct neurotoxic effects. (LLM, conf=0.84)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“transcriptomic profiling of infected kidney organoids aligned with the proteomic profile of the urine of individuals who were critically ill with COVID-19, further validating the findings of the model.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Could not verifycites [89] Jansen, J. et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell 29, 217–231.e8 (2022). sourceExperimental — accuracy not yet measured
The Results section reports RNA sequencing of infected kidney organoids and analysis of COVID-19 patient kidney tissue, but no passage reports comparing organoid transcriptomes with patients’ urine proteomes. Searches for “urine,” “proteomics,” and “urine proteome” found no such comparison in our copy, so the claimed alignment and resulting validation cannot be verified. (LLM, conf=0.74)
- Supportedcites [90] Helms, L. et al. Cross-validation of SARS-CoV-2 responses in kidney organoids and clinical populations. JCI Insight 6, e154882 (2021). source
The Results section ('COVID-19+ patient urine expresses signatures found in organoids') reports that urine proteins were analyzed in critically ill patients and that transcripts corresponding to 8 of 9 elevated urinary proteins also increased in infected kidney organoids. The Discussion says this shared signature supports the physiological relevance of the organoid findings. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“the antimalarial drugs chloroquine and hydroxychloroquine, which received controversial attention during the COVID-19 pandemic, proved non-effective in a human lung-on-chip disease model, similar to clinical findings51.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [51] Si, L. et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat. Biomed. Eng. 5, 815–829 (2021). source
The Results section ('Identification of approved drugs as SARS-CoV-2 entry inhibitors') reports that chloroquine and hydroxychloroquine had no effect on SARS-CoV-2 pseudovirus entry in human Airway Chips and notes that they also failed to show benefits in human clinical trials. The Discussion likewise says the chips predicted their lack of efficacy in human patients. The on-chip result concerns viral entry under the tested conditions, rather than every possible measure of drug efficacy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Organoids demonstrated the induction of inefficient interferon responses in SARS-CoV-2 infections84,85, revealing similar interferon signatures between SARS-CoV-2-infected bioengineered lung models and native human lungs”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [84] Katsura, H. et al. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Cell Stem Cell 27, 890–904.e8 (2020). sourceExperimental — accuracy not yet measured
The Results sections on IFN pathways and transcriptome-wide similarities report that infected alveolospheres activated interferon pathways and had strikingly similar IFN signatures to AT2 cells from COVID-19 patient lungs (page unavailable). The paper does not characterize the organoids’ interferon response as weak or inefficient; it reports significant upregulation of IFN-related transcripts, with inflammatory responses emerging at later times. (LLM, conf=0.85)
- Partly supportedcites [85] Lamers, M. M. et al. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J. 40, e105912 (2021). sourceExperimental — accuracy not yet measured
The Host responses section reports that SARS-CoV-2 infection induced a broad type I/III interferon-stimulated gene signature in the organoid-derived cultures. It does not characterize that response as weak or inefficient. The section compares the induction with a report on human bronchial epithelial cells, not with interferon signatures in native human lungs; no page number is available in our copy. (LLM, conf=0.84)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Treatment with the antibody TNT005, a specific complement component 1s inhibitor, inhibited the immune reaction and rescued the functional deficits, prompting the FDA to approve clinical trials (NCT04658472).”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Partly supportedcites [116] Rumsey, J. W. et al. Classical complement pathway inhibition in a “human-on-a-chip” model of autoimmune demyelinating neuropathies. Adv. Ther. 5, 2200030 (2022). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that TNT005 inhibited patient-serum-mediated complement deposition and rescued motoneuron functional deficits in the CIDP and MMN chip models. The Abstract says the efficacy data were included in an investigational new drug application, and the Introduction links the model to clinical testing (NCT04658472). Neither passage says the FDA approved trials because of these findings. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This endothelial dysfunction is exacerbated after the introduction of peripheral blood mononuclear cells, resulting in excessive inflammation82.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Supportedcites [82] Lu, R. X. Z. et al. Vasculature-on-a-chip platform with innate immunity enables identification of angiopoietin-1 derived peptide as a therapeutic for SARS-CoV-2 induced inflammation. Lab Chip 22, 1171–1186 (2022). source
The Discussion states that circulating PBMCs containing monocytes further exacerbated inflammatory responses and injury to endothelial barrier function in the SARS-CoV-2 infection model. This supports the citing sentence in that experimental context. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although some OoC models have been maintained for up to 3 months55, the effective lifetime of most disease models spans over a few days”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Partly supportedcites [55] Maschmeyer, I. et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip 15, 2688–2699 (2015). sourceExperimental — accuracy not yet measured
The citation follows the three-month claim. The Abstract and Introduction report that this four-organ-chip maintained functional co-cultures for at least 28 days, supporting long-term maintenance but not the stated three-month duration. The later claim about most disease models is not attached to this citation. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the similarity scaling approach140 adapts engineering techniques of dimensional analysis and similitude to OoCs. This strategy accounts for different similarity criteria (Box 1) simultaneously in a systematic framework”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Supportedcites [140] Feng, J. J. & Hedtrich, S. A similarity scaling approach for organ-on-chip devices. Lab Chip 22, 3663–3667 (2022). source
The opening section (p. 1) explicitly proposes a framework for OoCs adapted from dimensional analysis and similarity in engineering. The Similarity criteria section (p. 2) applies several criteria to OoCs, while Case studies (p. 2) says the approach accounts for parameters and their interactions systematically. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“microfabricated array devices using organoids at passage 0 provide drug screening results within a week without compromising the predictivity of patient responses to anticancer drugs152”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Supportedcites [152] Hu, Y. et al. Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week. Nat. Commun. 12, 2581 (2021). source
The Introduction says the microwell chip used passage-0 lung cancer organoids to test clinically recommended drugs within a week, without prolonged expansion. The Results report that the one-week on-chip tests agreed with evaluable patient responses, supporting the claim that the faster test retained predictive value. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mass spectrometry-based proteomics measures protein abundance and dynamics, identifies subcellular protein localization and post-transcriptional modifications, and facilitates the generation of interaction networks162”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Partly supportedcites [162] Kip, A. M. et al. Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury. Cell Death Dis. 12, 95 (2021). sourceExperimental — accuracy not yet measured
The Methods (Liquid chromatography mass spectrometry proteomics analysis; page unavailable) describe mass-spectrometry-based protein identification, and the Results (Differentiation of human small intestinal organoids; page unavailable) report protein abundance ratios. The Results (Temporal protein profiles; page unavailable) also track changes over time. Our copy does not show this approach identifying subcellular protein localization or post-transcriptional modifications, or generating protein interaction networks. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the medium circulation rate is disproportionately slow compared to physiological blood flow, which in turn slows down the transport of nutrients and metabolic processes in tissue models138”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Partly supportedcites [138] Sung, J. H., Wang, Y. & Shuler, M. L. Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems (MPS). APL Bioeng. 3, 021501 (2019). sourceExperimental — accuracy not yet measured
In “Scaling methods” (page not provided), the paper describes one liver–skin model whose medium recirculated more slowly than blood in the human body: 15 minutes versus about 5 minutes. In “Considerations for designing MPSs” (page not provided), it says perfusion affects nutrient supply and could alter biochemical reaction kinetics, but it does not establish that slow circulation generally slows nutrient transport and metabolic processes across tissue models. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it has proven difficult to balance competing key indices in multi-OoC setups; for a gut–liver system139, for example, a perfusion rate chosen for the gut to yield proper metabolic rates might result in drug exposure times in the liver that are too short”
§ Human disease models in drug development > Framework for disease model design > Model scaling
What the sources say
- Partly supportedcites [139] Maass, C., Stokes, C. L., Griffith, L. G. & Cirit, M. Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS). Integr. Biol. 9, 290–302 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“CDK4/6 inhibition also showed high in vitro and in vivo activity and synergy with anti-PD-1 blocking antibodies129.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
What the sources say
- Supportedcites [129] Deng, J. et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 8, 216–233 (2018). source
The Results section reports that CDK4/6 inhibition combined with anti-PD-1 synergistically induced cell death in cultured tumor spheroids. It also reports that the combination outperformed either treatment alone in murine tumors, supporting the claimed activity and synergy. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, organoids can be cultivated over months and probably even years, thus enabling the investigation of tissue maturation in a disease context as shown for SARS-CoV-2 infections in brain organoids87”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Partly supportedcites [87] Ramani, A. et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 39, e106230 (2020). sourceExperimental — accuracy not yet measured
The Results section reports that 60-day-old brain organoids showed signs of maturation and had more SARS-CoV-2-positive cells than 15-day-old organoids. This supports using organoids of different maturities to study infection, but the paper does not establish cultivation over years or investigation of tissue maturation during a prolonged infection; the Discussion says experiments with more mature organoids are still needed. Page numbers are unavailable in our copy. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“these models mainly focus on preclinical safety testing and not disease modelling and are not customizable169”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
What the sources say
- Partly supportedcites [169] Busek, M., Aizenshtadt, A., Amirola-Martinez, M., Delon, L. & Krauss, S. Academic user view: organ-on-a-chip technology. Biosensors 12, 126 (2022). sourceExperimental — accuracy not yet measured
The Discussion (p. 7) says most commercial organ-on-chip platforms are tailored for pharmaceutical testing and only a few are suitable for disease modelling. The paper does not narrow that focus to preclinical safety testing: the Overview (p. 3) discusses both safety and efficacy. The opening summary (p. 1) says self-made systems offer opportunities for customized models, but does not establish that commercial systems cannot be customized. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“broad clinical implementation of patient-specific disease models, such as PDOs, is currently hindered by low efficiencies in PDO establishment (60–70% success rate on average although, for some tissues, up to 90% have been reported for intestinal organoids151) as well as lengthy generation times and expansion procedures”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
What the sources say
- Supportedcites [151] van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Spatial profiling provides further information on tissue organization and three-dimensional architecture, thereby being essential for model validation186,187”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
What the sources say
- Partly supportedcites [186] Fleck, J. S. et al. Resolving organoid brain region identities by mapping single-cell genomic data to reference atlases. Cell Stem Cell 28, 1148–1159.e8 (2021). sourceExperimental — accuracy not yet measured
The Results ('Spatial projection of organoid cell transcriptomes'; page not available) show that mapping organoid cells to a spatial brain atlas helps assess regional identity and can be visualized in three dimensions. The paper does not show that this profiling reveals the organoid tissue’s own three-dimensional architecture, or establish that it is essential for model validation. (LLM, conf=0.84)
- Partly supportedcites [187] Rodriques, S. G. et al. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363, 1463–1467 (2019). sourceExperimental — accuracy not yet measured
The paper’s main text (page unavailable in our copy) shows that Slide-seq resolves tissue organization and that co-registered hippocampal sections allow three-dimensional visualization. It does not say that spatial profiling is essential for model validation. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“most models rely on the integration of only a few, pre-defined immune cell types, which, however, does not emulate the complexity of in vivo immunoregulation”
§ Human disease models in drug development > Challenges and limitations > Immunoregulation
What the sources say
- Partly supportedcites [143] Huh, D. et al. Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010). sourceExperimental — accuracy not yet measured
The Abstract (page not provided) says existing models fail to recreate an interface important for immune-cell transport. The Biomimetic Microsystems section (page not provided) acknowledges that this lung chip lacks alveolar macrophages. These passages support a limitation in modeling immune responses, but do not establish that most disease models integrate only a few pre-defined immune cell types. (LLM, conf=0.80)
- Partly supportedcites [145] Bein, A. et al. Enteric coronavirus infection and treatment modeled with an immunocompetent human intestine-on-a-chip. Front. Pharmacol. 12, 718484 (2021). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says patient-derived intestinal organoids lack circulating immune cells and other features of the in vivo organ environment, supporting the concern that such models miss physiological complexity. It does not say that most disease models integrate only a few predefined immune cell types. (LLM, conf=0.78)
- Partly supportedcites [154] Wallmeyer, L. et al. TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents. Sci. Rep. 7, 774 (2017). sourceExperimental — accuracy not yet measured
The Introduction says some earlier inflammatory-skin models used disease-associated cytokines but lacked actual immune cells, so they could not fully reflect complex skin–immune interactions. It does not establish that most disease models integrate a few pre-defined immune cell types; the examples it describes contain no immune cells. (LLM, conf=0.83)
- Supportedcites [155] Maharjan, S., Cecen, B. & Zhang, Y. S. 3D immunocompetent organ-on-a-chip models. Small Methods 4, 2000235 (2020). source
The Concluding remarks and perspectives section says most OOC devices capture only simplified immune components, such as macrophages or neutrophils, rather than the broader immune repertoire. The Immune organ-on-a-chip section adds that models using one or a few immune components provide limited information and calls for platforms that emulate more complex immune tissues. (LLM, conf=0.91)
- Partly supportedcites [156] Kerns, S. J. et al. Human immunocompetent Organ-on-Chip platforms allow safety profiling of tumor-targeted T-cell bispecific antibodies. eLife 10, e67106 (2021). sourceExperimental — accuracy not yet measured
The Introduction says conventional 2D models lack the complexity needed to model immunotherapeutic effects and omit essential cellular factors. The Discussion says accurately modeling multifactorial immune-related toxicities would likely require resident immune cells and lymphoid structures. Neither passage establishes that most disease models integrate only a few pre-defined immune cell types. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“‘living biobanks’ can provide access to patient-derived cells and organoids from large patient cohorts, and have already been established for different cancers124,151,176–178, genetic diseases such as cystic fibrosis, infectious diseases, chronic obstructive pulmonary disease and inflammatory bowel diseases179”
§ Human disease models in drug development > Outlook
What the sources say
- Partly supportedcites [124] Lee, S. H. et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173, 515–528.e17 (2018). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [151] van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [176] Yan, H. H. N. et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell 23, 882–897.e11 (2018). source
- Not checked — no full text of the sourcecites [177] Sachs, N. et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell 172, 373–386.e10 (2018). source
- Supportedcites [178] Jacob, F. et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell 180, 188–204.e22 (2020). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [179] Ramalho, A. S. et al. Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis. Eur. Respir. J. 57, 1902426 (2021). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ClinicalTrials.gov currently lists 131 studies for the search term ‘organoids’, most of which focus on cancer.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“they have limited cell diversity and lack self-renewal capacity in non-stem cell-based models.”
§ Human disease models in drug development > Overview of human disease models > Bioengineered tissue models
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“efforts are ongoing to develop bioengineered human-based (disease) models of high clinical biomimicry to close this translational gap.”
§ Human disease models in drug development > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The discrepancies derive from different anatomical layouts and biological barriers, divergent receptor expression and immune responses, host specificities of microorganisms, and distinct pathomechanisms.”
§ Human disease models in drug development > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“these tissue models cannot be cryopreserved or propagated and therefore have a limited lifespan.”
§ Human disease models in drug development > Overview of human disease models > Bioengineered tissue models
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ASC-derived organoids lack cells from the ectodermal and mesenchymal germ layer and are usually smaller than iPS cell-derived counterparts.”
§ Human disease models in drug development > Overview of human disease models > Organoids
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Engineered cells, such as reporter cell lines, are also commonly used as they are amenable to high-throughput manufacturing and have high reproducibility and lower costs relative to stem cell-based methods.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Primary cells are the preferred option owing to their higher genetic heterogeneity compared to cell lines, but their limited availability or in vitro proliferation capacity restricts their use.”
§ Human disease models in drug development > Overview of human disease models > 2D cell cultures
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Currently, 40% of the drugs undergoing clinical trials are antibodies3.”
§ Human disease models in drug development > Introduction
What the sources say
- Not matchedcites [3] IQVIA Institute. Global Trends in R&D 2022 (IQVIA Institute, 2021).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Infection studies using human ASC-derived intestinal organoids provided the solution as they closely emulate the host environment by differentiating into physiologically active, multicellular epithelial tissues.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [96] Ettayebi, K. et al. Replication of human noroviruses in stem cell-derived human enteroids. Science 353, 1387–1393 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The efficacy of the lead compounds was assessed in iPS cell-derived motor neurons showing splice correction and restored protein levels.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“rectal organoids from 71 individuals with cystic fibrosis that harboured 28 different CFTR mutations revealed residual CFTR function and identified effective drug combinations.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
plaindirectn = 71- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Risdiplam received its marketing authorization in the EU in 2021 and became the first orally available medication for spinal muscular atrophy.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This system revealed that C. neoformans trespasses the blood–brain barrier through transcytosis, providing a potential therapeutic target to inhibit this process104.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [104] Kim, J. et al. Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier. Nat. Biomed. Eng. 5, 830–846 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These findings relied entirely on human-derived cancer organoids and went from bench to bedside in just 3 years (NCT03526835)114.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [114] Herpers, B. et al. Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat. Cancer 3, 418–436 (2022). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“measuring the lumen area of the organoids allowed comparison of CFTR function among patients, thereby providing physicians with a reliable predicting tool for clinical decision-making.”
§ Human disease models in drug development > Preclinical and clinical applications > Clinical research
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These results were replicated in clinical trials (for example, NCT04538664), eventually leading to the approval of amivantamab by the EMA for the treatment of non-small cell lung cancer.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [115] Yun, J. et al. Antitumor activity of Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in diverse models of EGFR exon 20 insertion-driven NSCLC. Cancer Discov. 10, 1194–1209 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“infection studies in brain organoids showed that the Zika virus primarily infects neural progenitor cells, which increases neural cell death and reduces proliferation, thereby hampering neurogenesis and causing microcephaly99,100.”
§ Human disease models in drug development > Preclinical and clinical applications > Preclinical research
What the sources say
- Not checked — no full text of the sourcecites [99] Qian, X. et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238–1254 (2016). source
- Not checked — no full text of the sourcecites [100] Garcez, P. P. et al. Zika virus impairs growth in human neurospheres and brain organoids. Science 352, 816–818 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If the goal is to unravel disease mechanisms or study drug efficacy and safety, disease models with higher biomimicry and complexity are required”
§ Human disease models in drug development > Framework for disease model design
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient-specific disease models hold great potential for personalized and precision medicine”
§ Human disease models in drug development > Preclinical and clinical applications > Future applications in clinical trials
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The problem is further aggravated by variabilities in model composition, complexity and experimental protocols”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“commercially available setups are often still very expensive and therefore not affordable for many laboratories”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“single-cell proteomics is still in its infancy; measurements are time consuming, expensive and have a limited dynamic range of measurements, rendering it low throughput”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“rigorous disease model validation is essential but often neglected”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Putative key components, such as cells or biomechanical cues relevant to the disease of interest, are included based on existing knowledge, yet the possibility to overlook and thus exclude disease-relevant contributors remains. This biased approach bears the risk of false-positive or false-negative results”
§ Human disease models in drug development > Challenges and limitations > Limited complexity
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Human-based models from both sexes and different ethnicities could help pinpoint these inter-individual differences, thereby improving therapeutic assessment.”
§ Human disease models in drug development > Preclinical and clinical applications > Future applications in clinical trials
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Media mixtures are typically used in these models, which, however, could reverse tissue maturation because cells from different germ layers are exposed to unspecific factors. This mismatch could result in gene and protein expression levels that are atypical for the tissue of interest”
§ Human disease models in drug development > Challenges and limitations > Limited lifespan and long cultivation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These two methods account for length and mass scales but not the time scale, and are often inaccurate”
§ Human disease models in drug development > Framework for disease model design > Model scaling
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Miniaturized models typically carry fewer cells and lack a pervasive vasculature to perfuse the tissue compared to actual organs”
§ Human disease models in drug development > Framework for disease model design > Model scaling
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Developing and maintaining bioengineered disease models require high-level expertise and costly infrastructures”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“providing a universal disease model design is challenging because their usefulness is strongly context dependent and influenced by the intended use and relevant readout parameters”
§ Human disease models in drug development > Framework for disease model design
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“when studying systemic conditions such as inflammation or metastatic cancer, complex multi-OoC setups are superior to single-tissue or organ models”
§ Human disease models in drug development > Framework for disease model design
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar to bulk RNA-seq, proteomic analysis at the bulk level provides a population average and obscures cellular heterogeneities”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Women are often underrepresented, partly owing to the risk of reproductive toxicity.”
§ Human disease models in drug development > Preclinical and clinical applications > Future applications in clinical trials
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“2D high-throughput methods using patient-specific or genetically engineered cells are most suitable as they allow testing of a large number of compounds in a short time”
§ Human disease models in drug development > Framework for disease model design
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These combinatorial approaches could help identify effective drugs more reliably, although their actual impact has yet to be proven”
§ Human disease models in drug development > Challenges and limitations > Disease model validation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is unrealistic to assume that the complexity of a human can be fully recapitulated in vitro”
§ Human disease models in drug development > Outlook
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“personalized disease models are well suited for clinical decision-making and in clinical trials to diversify the patient cohorts with respect to ethnicity, sex or age”
§ Human disease models in drug development > Outlook
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Some OoC setups have the size of a coin (or even smaller), thereby making it difficult to cultivate actual 3D tissue models”
§ Human disease models in drug development > Challenges and limitations > Commercialization and accessibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“initial drawbacks, such as the lack of cell diversity, vascularization and the ability to study tissue crosstalk, have already been largely overcome”
§ Human disease models in drug development > Outlook
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“animal models are still considered the gold standard and therefore are often requested by default by grant review panels or reviewers”
§ Human disease models in drug development > Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Animal testing is not going to be completely replaced in the near future for several reasons, one of them being that toxicity testing in animals is legally mandated before entering clinical trials”
§ Human disease models in drug development > Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“different disease models are suitable for different applications; organoids, for example, are useful for high-throughput drug screenings, whereas OoCs are more applicable for drug safety and efficacy testing”
§ Human disease models in drug development > Outlook
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“they are poorly suited for high-throughput screenings”
§ Human disease models in drug development > Outlook
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
The decision to enter a drug candidate into clinical trials depends almost entirely on animal-derived data.
“the decision on entry of a drug candidate into clinical trials relies almost exclusively on animal-derived data.”
The paper relies on this without support.
The human brain has an additional cortical layer containing radial glial progenitor cells.
“the human brain has an additional cortical layer containing radial glial cells (progenitor cells).”
The paper relies on this without support.
Animal models are the only preclinical systems that allow study of disease mechanisms and drug effects in the complex environment of a living organism.
“Animal models are the only preclinical systems that allow the study of disease mechanisms and drug effects in the complex environment of a living organism”
The paper relies on this without support.
The FDA Modernization Act 2.0 has broadened the scope of accepted preclinical models and encourages scientists to test drug efficacy and safety in human models whenever possible.
“the FDA Modernization Act 2.0 has further broadened the scope of accepted preclinical models and encourages scientists to test drug efficacy and safety in human models whenever possible”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Cell based and bioinspired carriers remain compelling for specific niches, for example blood–brain barrier delivery, immune cell trafficking and homologous adhesion, but their translational pathway depends as much on standardized sourcing, potency assays and regulatory alignment as on delivery performance [131].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [131]
Experimental — accuracy not yet measured
Citations
Cites
Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372
Reconstituting organ-level lung functions on a chip
Huh, D., Matthews, B. D., Mammoto, A., Montoya-Zavala, M., Hsin, H. Y., & Ingber, D. E. (2010) · Science · doi:10.1126/science.1188302 · Cited by 4,250
Sato, T., Stange, D. E., Ferrante, M., Vries, R. G. J., van Es, J. H., van den Brink, S., van Houdt, W. J., Pronk, A., van Gorp, J., Siersema, P. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.050 · Cited by 3,753
Vepari, C., & Kaplan, D. L. (2007) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.05.013 · Cited by 2,579
Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution
Rodriques, S. G., Stickels, R. R., Goeva, A., Martin, C. A., Murray, E., Vanderburg, C. R., Welch, J., Chen, L. M., Chen, F., & Macosko, E. Z. (2019) · Science · doi:10.1126/science.aaw1219 · Cited by 2,424
Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients
van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. (2015) · Cell · doi:10.1016/j.cell.2015.03.053 · Cited by 2,408
Vascularized and functional human liver from an iPSC-derived organ bud transplant
Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. (2013) · Nature · doi:10.1038/nature12271 · Cited by 2,170
Organoid models of human and mouse ductal pancreatic cancer
Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.032 · Cited by 2,127
Research works printed but not linked: 1
- Bai, H. et al. Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip. Nat. Commun. 13, 1928 (2022). · DOI · Paper page
Cited by
Sorted by citations
Neuropathogenesis-on-chips for neurodegenerative diseases
Amartumur, S., Nguyen, H. M., Huynh, T., Kim, T. S., Woo, R., Oh, E., Kim, K. K., Lee, L. P., & Heo, C. (2024) · Nature Communications · doi:10.1038/s41467-024-46554-8 · Cited by 131
Navigating the complexities of drug development for inflammatory bowel disease
Honap, S., Jairath, V., Danese, S., & Peyrin‐Biroulet, L. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00953-0 · Cited by 123
“Integrating omics techniques with a systems biology approach to handle high-volume data from organoids would almost certainly accelerate development 153 .”
Lithography-based 3D printing of hydrogels
Dhand, A. P., Davidson, M. D., & Burdick, J. A. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00251-9 · Cited by 114
“In addition to screening, in vitro 3D systems can model healthy or diseased tissues to study development and disease progression 136 .”
Application of Artificial Intelligence In Drug-target Interactions Prediction: A Review
Liao, Q., Zhang, Y., Chu, Y., Ding, Y., Liu, Z., Zhao, X., Wang, Y., Wan, J., Ding, Y., Tiwari, P., et al. (2025) · npj Biomedical Innovations · doi:10.1038/s44385-024-00003-9 · Cited by 82
Ultrasound-assisted tissue engineering
Melde, K., Athanassiadis, A. G., Missirlis, D., Shi, M., Seneca, S., & Fischer, P. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00166-5 · Cited by 59
Metadata
- Authors
- Loewa, A., Feng, J. J., & Hedtrich, S.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Hedtrich, Sarah
- Venue
- Nature Reviews Bioengineering
- Published
- 2023-05-11
- Volume
- 1
- Issue
- 8
- Pages
- 545-559
- ISSN
- 2731-6092 (ISSN-L)
- PMC
- PMC10173243
- OpenAlex
- W4376136225
- Cited by
- 331
- References
- 193
- Citations by year
- 2026: 107 · 2025: 126 · 2024: 85 · 2023: 13
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-06-13)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Bioengineering (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (project A05))
- Stiftung Charité
- Natural Sciences and Engineering Research Council of Canada (RGPIN 2020, rgpin-2020-04224, 2019-04162, rgpin-2019-04162, 2020-04224, RGPIN-2019)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- human disease models, drug development, organoids, organ-on-a-chip, translational research, animal model limitations, clinical translation, preclinical models
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
