The DOI matches its Crossref record; 245 of the 245 references it cites were found in a registry or an index.
Human biomimetic liver microphysiology systems in drug development and precision medicine
Open accessAbstract
Microphysiology systems (MPS), also called organs-on-chips and tissue chips, are miniaturized functional units of organs constructed with multiple cell types under a variety of physical and biochemical environmental cues that complement animal models as part of a new paradigm of drug discovery and development. Biomimetic human liver MPS have evolved from simpler 2D cell models, spheroids and organoids to address the increasing need to understand patient-specific mechanisms of complex and rare diseases, the response to therapeutic treatments, and the absorption, distribution, metabolism, excretion and toxicity of potential therapeutics. The parallel development and application of transdisciplinary technologies, including microfluidic devices, bioprinting, engineered matrix materials, defined physiological and pathophysiological media, patient-derived primary cells, and pluripotent stem cells as well as synthetic biology to engineer cell genes and functions, have created the potential to produce patient-specific, biomimetic MPS for detailed mechanistic studies. It is projected that success in the development and maturation of patient-derived MPS with known genotypes and fully matured adult phenotypes will lead to advanced applications in precision medicine. In this Review, we examine human biomimetic liver MPS that are designed to recapitulate the liver acinus structure and functions to enhance our knowledge of the mechanisms of disease progression and of the absorption, distribution, metabolism, excretion and toxicity of therapeutic candidates and drugs as well as to evaluate their mechanisms of action and their application in precision medicine and preclinical trials.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“The goal of HBL-MPS is to accurately represent the structure and function of the hepatic lobule, including oxygen gradients, zonation, vascularization, and cell signaling (Fig. 10A) [179].”
From Constructing biomimetic microenvironments for liver regeneration (2025) · cites this paper as [179]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
WITHDRAWN—a resource for withdrawn and discontinued drugs
Siramshetty, V. B., Nickel, J., Omieczynski, C., Gohlke, B.-O., Drwal, M. N., & Preissner, R. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1192 · Cited by 286
RetractedMechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286
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
Singh, S., Allen, A. M., Wang, Z., Prokop, L. J., Murad, M. H., & Loomba, R. (2015) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2014.04.014 · Cited by 1,748
Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver
Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M. A., Ellis, E., van Wenum, M., Fuchs, S. A., de Ligt, J., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.050 · Cited by 1,619
Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018
Wouters, O. J., McKee, M., & Luyten, J. (2020) · JAMA · doi:10.1001/jama.2020.1166 · Cited by 1,531
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525
Organoids as an in vitro model of human development and disease
Fatehullah, A., Tan, S. H., & Barker, N. (2016) · Nature Cell Biology · doi:10.1038/ncb3312 · Cited by 1,508
Research works printed but not linked: 1
- European Medicines Agency. Meeting Report: First EMA workshop on non-animal approaches in support of medicinal product development – challenges and opportunities for use of micro-physiological systems (EMA/CHMP/SWP/250438/2018) (European Medicines Agency, 2018).
Cited by
Sorted by citations
Mechanical communication in fibrosis progression
Long, Y., Niu, Y., Liang, K., & Du, Y. (2022) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.10.002 · Cited by 233
Organs-on-chips technologies – A guide from disease models to opportunities for drug development
Monteduro, A. G., Rizzato, S., Caragnano, G., Trapani, A., Giannelli, G., & Maruccio, G. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115271 · Cited by 193
Liver organ-on-chip models for toxicity studies and risk assessment
Messelmani, T., Morisseau, L., Sakai, Y., Legallais, C., Goff, A. L., Leclerc, É., & Jellali, R. (2022) · Lab on a Chip · doi:10.1039/d2lc00307d · Cited by 113
Bertassoni, L. E. (2021) · Advanced Materials · doi:10.1002/adma.202101321 · Cited by 98
Immune-mediated drug-induced liver injury: immunogenetics and experimental models
Gerussi, A., Natalini, A., Antonangeli, F., Mancuso, C., Agostinetto, E., Barisani, D., Di Rosa, F., Andrade, R., & Invernizzi, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094557 · Cited by 87
Metadata
- Authors
- Gough, A., Soto-Gutierrez, A., Vernetti, L., Ebrahimkhani, M. R., Stern, A. M., & Taylor, D. L.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Taylor, D. Lansing
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2020-12-17
- Volume
- 18
- Issue
- 4
- Pages
- 252-268
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC9106093
- OpenAlex
- W3112962917
- Cited by
- 117
- References
- 245
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 21 · 2023: 20 · 2022: 19 · 2021: 16
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UG3TR003289, U01TR002383)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK117881)
- National Center for Advancing Translational Sciences
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- organ-on-a-chip, microphysiological systems, drug development, precision medicine, liver acinus, microfluidics, bioprinting, organoids, spheroids, pluripotent stem cells, synthetic biology, patient-specific disease models
- MeSH terms
- Drug Development, Drug Evaluation, Preclinical, Humans, Liver, Models, Animal, Biomimetics, Microfluidics, Microchip Analytical Procedures, Lab-On-A-Chip Devices, Precision Medicine
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.
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