Human organs-on-chips for disease modelling, drug development and personalized medicine
Open accessAbstract
The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology with high fidelity. Here, I review how single and multiple human organ chip systems have been used to model complex diseases and rare genetic disorders, to study host–microbiome interactions, to recapitulate whole-body inter-organ physiology and to reproduce human clinical responses to drugs, radiation, toxins and infectious pathogens. I also address the challenges that must be overcome for organ chips to be accepted by the pharmaceutical industry and regulatory agencies, as well as discuss recent advances in the field. It is evident that the use of human organ chips instead of animal models for drug development and as living avatars for personalized medicine is ever closer to realization. This Review discusses the types of single and multiple human organ-on-a-chip (organ chip) microfluidic devices and their diverse applications for disease modelling, drug development and personalized medicine, as well as the challenges that must be overcome for organ chips to reach their full potential.
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Most animal models resemble human conditions poorly and therefore predict poorly.
“most animal models poorly resemble human conditions and thus have low predictive values.”
From Human disease models in drug development (2023) · cites this paper as [6]
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)
Experimental — accuracy not yet measuredOrgans-on-chips are perfused microfluidic devices with engineered or miniaturized tissues linked by 3D microchannels to mimic organ functions, biomechanics and pathophysiological responses.
“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.”
From Human disease models in drug development (2023) · cites this paper as [6]
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)
Experimental — accuracy not yet measuredAnimal models frequently do not screen out drugs that are harmful or ineffective.
“Animal models, however, often fail to filter out harmful or ineffective drugs6.”
From Human disease models in drug development (2023) · cites this paper as [6]
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Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk
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Self-citationEffects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function
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Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development
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Impact of organ-on-a-chip technology on pharmaceutical R&D costs
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Self-citationSARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip
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Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip
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Self-citationClear castable polyurethane elastomer for fabrication of microfluidic devices
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Self-citationA Microengineered Airway Lung Chip Models Key Features of Viral-induced Exacerbation of Asthma
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Three-dimensional microengineered vascularised endometrium-on-a-chip
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Biomechanical Strain Exacerbates Inflammation on a Progeria‐on‐a‐Chip Model
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Autologous Induced Pluripotent Stem Cell-Derived Four-Organ-Chip
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Wet‐AMD on a Chip: Modeling Outer Blood‐Retinal Barrier In Vitro
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A 3D human renal cell carcinoma-on-a-chip for the study of tumor angiogenesis
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Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
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Human Nonalcoholic Steatohepatitis on a Chip
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Differential Monocyte Actuation in a Three‐Organ Functional Innate Immune System‐on‐a‐Chip
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Laminar ventricular myocardium on a microelectrode array-based chip
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Metal‐Specific Biomaterial Accumulation in Human Peri‐Implant Bone and Bone Marrow
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In vitro test systems and their limitations
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Forensic Analysis of Human Microbiome in Skin and Body Fluids Based on Geographic Location
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A Personalized Glomerulus Chip Engineered from Stem Cell-Derived Epithelium and Vascular Endothelium
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Construction of a high fidelity epidermis-on-a-chip for scalable in vitro irritation evaluation
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Biomaterial and Biofilm Interactions with the Pulp-Dentin Complex-on-a-Chip
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A directional 3D neurite outgrowth model for studying motor axon biology and disease
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Microphysiological Systems: Stakeholder Challenges to Adoption in Drug Development
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Clinically Relevant Influenza Virus Evolution Reconstituted in a Human Lung Airway-on-a-Chip
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Transferrin receptor targeting by de novo sheet extension
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Self-citationMicrofluidic Model for Evaluation of Immune Checkpoint Inhibitors in Human Tumors
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Microphysiological flux balance platform unravels the dynamics of drug induced steatosis
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Self-citationEndothelial Thermotolerance Impairs Nanoparticle Transport in Tumors
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Self-citationThree-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment
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Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity
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Self-citationA 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy
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Advances in Engineered Three-Dimensional (3D) Body Articulation Unit Models
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Glucocorticoid Clearance and Metabolite Profiling in an In Vitro Human Airway Epithelium Lung Model
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Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours
Flugel, C. L., Majzner, R. G., Krenciute, G., Dotti, G., Riddell, S. R., Wagner, D. L., & Abou‐El‐Enein, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00704-3 · Cited by 571 · see citing works
Fecal microbiota transplantation: current challenges and future landscapes
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- Authors
- Ingber, D. E.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Ingber, Donald E.
- ORCID
- Ingber, Donald E.
- Venue
- Nature Reviews Genetics
- Published
- 2022-03-25
- Volume
- 23
- Issue
- 8
- Pages
- 467-491
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC8951665
- OpenAlex
- W4220652963
- Cited by
- 1,589
- References
- 151
- Citations by year
- 2026: 457 · 2025: 440 · 2024: 389 · 2023: 215 · 2022: 87 · 2018: 1
- FWCI
- 25.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Reviews Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bill and Melinda Gates Foundation
- National Institutes of Health
- Defense Advanced Research Projects Agency
- Biomedical Advanced Research and Development Authority
- National Heart, Lung, and Blood Institute (UH3HL141797)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- organ-on-a-chip, microfluidics, disease modeling, drug development, personalized medicine, alternative to animal models, rare genetic disorders, host-microbiome interactions, drug toxicity, infectious agents, regulatory acceptance, pharmaceutical industry
- MeSH terms
- Drug Development, Animals, Humans, Rare Diseases, Lab-On-A-Chip Devices, Precision Medicine
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