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.
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“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]
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Items 201–245 of 245
Non-alcoholic fatty liver disease: a narrative review of genetics
Christopher, J., Zemin, Y., & Jiang, Z. G. (2018) · Journal of Biomedical Research · doi:10.7555/jbr.32.20180045 · Cited by 46
Programming Morphogenesis through Systems and Synthetic Biology
Velazquez, J. J., Su, E. Y., Cahan, P., & Ebrahimkhani, M. R. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.11.003 · Cited by 45
Self-citationMoat, S. J., Schulenburg‐Brand, D., Lemonde, H. A., Bonham, J. R., Weykamp, C. W., Mei, J. V., Shortland, G., & Carling, R. S. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12163 · Cited by 44
Bricks, T., Hamon, J., Fleury, M. J., Jellali, R., Merlier, F., Herpe, Y.-É., Seyer, A., Regimbeau, J., Bois, F. Y., & Leclerc, É. (2015) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.1940 · Cited by 43
Peck, R., Hinojosa, C. D., & Hamilton, G. A. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1688 · Cited by 42
Applications of the microphysiology systems database for experimental ADME-Tox and disease models
Schurdak, M. E., Vernetti, L. A., Bergenthal, L., Wolter, Q. K., Shun, T. Y., Karcher, S. C., Taylor, D. L., & Gough, A. (2020) · Lab on a Chip · doi:10.1039/c9lc01047e · Cited by 41
Self-citationRoles of Hepatic Drug Transporters in Drug Disposition and Liver Toxicity
Pan, G. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-7647-4_6 · Cited by 40
Microphysiological flux balance platform unravels the dynamics of drug induced steatosis
Ehrlich, A., Tsytkin-Kirschenzweig, S., Ioannidis, K., Ayyash, M., Riu, A., Note, R., Ouédraogo, G., Vanfleteren, J., Cohen, M., & Nahmias, Y. (2018) · Lab on a Chip · doi:10.1039/c8lc00357b · Cited by 38
Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury
Donato, M. T., & Tolosa, L. (2019) · Differentiation · doi:10.1016/j.diff.2019.02.004 · Cited by 38
Macrophages in Nonalcoholic Steatohepatitis: Friend or Foe?
Grunhut, J., Wang, W., Aykut, B., Gakhal, I., Torres-Hernandez, A., & Miller, G. (2018) · EMJ Hepatology · doi:10.33590/emjhepatol/10312252 · Cited by 38
Bioengineered models to study tumor dormancy
Rao, S. S., Kondapaneni, R. V., & Narkhede, A. A. (2019) · Journal of Biological Engineering · doi:10.1186/s13036-018-0137-0 · Cited by 37
Organoids, organs-on-chips and other systems, and microbiota
May, S., Evans, S., & Parry, L. (2017) · Emerging Topics in Life Sciences · doi:10.1042/etls20170047 · Cited by 36
Gough, A., Vernetti, L. A., Bergenthal, L., Shun, T. Y., & Taylor, D. L. (2016) · Applied In Vitro Toxicology · doi:10.1089/aivt.2016.0011 · Cited by 36
Self-citationHuman three-dimensional in vitro model of hepatic zonation to predict zonal hepatotoxicity
Ahn, J.-H., Ahn, J., Yoon, S., Nam, Y. S., Son, M., & Oh, J. (2019) · Journal of Biological Engineering · doi:10.1186/s13036-019-0148-5 · Cited by 36
Hormone and Drug-Mediated Modulation of Glucose Metabolism in a Microscale Model of the Human Liver
Davidson, M. D., Lehrer, M., & Khetani, S. R. (2014) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2014.0512 · Cited by 34
Mullard, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-020-00126-9 · Cited by 34
Terelius, Y., Figler, R. A., Marukian, S., Collado, M. S., Lawson, M. J., Mackey, A. J., Manka, D., Qualls, C. W., Blackman, B. R., Wamhoff, B. R., et al. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2015.11.023 · Cited by 33
Parent, R., Durantel, D., Lahlali, T., Sallé, A., Plissonnier, M., DaCosta, D., Lesca, G., Zoulim, F., Marion, M., & Bartosch, B. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.05.038 · Cited by 33
Hughes, D. J., Kostrzewski, T. M., & Sceats, E. L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217708976 · Cited by 33
Fluorescent protein biosensors applied to microphysiological systems
Senutovitch, N., Vernetti, L. A., Boltz, R. C., DeBiasio, R., Gough, A., & Taylor, D. L. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215584934 · Cited by 32
Self-citationNonalcoholic fatty liver disease
Pοlyzos, S. A., Kountouras, J., Anastasiadis, S., Doulberis, M., & Katsinelos, P. (2018) · Hepatology · doi:10.1002/hep.29897 · Cited by 31
Tackling rare diseases: Clinical trials on chips
Blumenrath, S. H., Lee, B. Y., Low, L. A., Prithviraj, R., & Tagle, D. A. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220924743 · Cited by 28
Acute Liver Failure: Review and Update
Bernal, W. E. (2017) · International Anesthesiology Clinics · doi:10.1097/aia.0000000000000141 · Cited by 28
Taylor, D. L., Gough, A., Schurdak, M. E., Vernetti, L. A., Chennubhotla, C. S., Lefever, D. E., Pei, F., Faeder, J. R., Lezon, T. R., Stern, A. M., et al. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_239 · Cited by 28
Self-citationPennisi, G., Celsa, C., Spatola, F., Dallio, M., Federico, A., & Petta, S. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16224334 · Cited by 25
Menon, V., Lincoff, A. M., Nicholls, S. J., Jasper, S. E., Wolski, K., McGuire, D. K., Mehta, C. R., Rosenstock, J., Lopez, C. M., MARCINAK, J. F., et al. (2018) · Diabetes Care · doi:10.2337/dc18-0755 · Cited by 24
Miedel, M. T., Gavlock, D. C., Jia, S., Gough, A., Taylor, D. L., & Stern, A. M. (2019) · Scientific Reports · doi:10.1038/s41598-019-44756-5 · Cited by 24
Self-citationLeclerc, É., Kimura, K., Shinohara, M., Danoy, M., Gall, M. L., Kido, T., Miyajima, A., Fujii, T., & Sakai, Y. (2016) · Genomics · doi:10.1016/j.ygeno.2016.11.008 · Cited by 23
Proteostasis Strategies for Restoring α1-Antitrypsin Deficiency
Bouchecareilh, M., Conkright, J. J., & Balch, W. E. (2010) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201001-016aw · Cited by 21
Pei, F., Li, H., Henderson, M. J., Titus, S. A., Jadhav, A., Simeonov, A. M., Çobanoğlu, M. C., Mousavi, S. H., Shun, T., McDermott, L. A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17378-y · Cited by 21
Self-citationCholangiocytes derived from induced pluripotent stem cells for disease modeling
Ghanekar, A., & Kamath, B. M. (2016) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000260 · Cited by 20
Jia, S., Miedel, M. T., Ngo, M., Hessenius, R., Chen, N., Wang, P., Bahreini, A., Li, Z., Ding, Z., Shun, T. Y., et al. (2018) · Oncology · doi:10.1159/000485510 · Cited by 20
Self-citationCorrections of Molecular Morphology and Hydrogen Bond for Improved Crystal Density Prediction
Wang, L., Zhang, M., Chen, J., Su, L., Zhao, S., Zhang, C., Liu, J., & Chen, C. (2019) · Molecules · doi:10.3390/molecules25010161 · Cited by 20
The Design and Application of Genetically Encodable Biosensors Based on Fluorescent Proteins
Newman, R. H., & Zhang, J. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-622-1_1 · Cited by 17
Microphysiological Systems (Tissue Chips) and their Utility for Rare Disease Research
Low, L. A., & Tagle, D. A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67144-4_23 · Cited by 17
Pharmacokinetic-based multi-organ chip for recapitulating organ interactions
Sung, J. H. (2018) · Methods in cell biology · doi:10.1016/bs.mcb.2018.05.008 · Cited by 16
Generation of Antigen-Specific T Cells from Human Induced Pluripotent Stem Cells
Nishimura, T., & Nakauchi, H. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-8938-6_3 · Cited by 16
Microphysiological Systems: automated fabrication via extrusion bioprinting
Prendergast, M. E., Montoya, G. A., Pereira, T., Lewicki, J., Solorzano, R., & Atala, A. (2018) · Microphysiological Systems · doi:10.21037/mps.2018.03.01 · Cited by 12
The great escape: How metastases of melanoma, and other carcinomas, avoid elimination
Wells, A. H., Clark, A. M., Bradshaw, A. M., Ma, B., & Edington, H. J. D. (2018) · Experimental Biology and Medicine · doi:10.1177/1535370218820287 · Cited by 12
COVID-19 platform trial delivers
Mullard, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-020-00128-7 · Cited by 11
Mullard, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/d41573-020-00127-8 · Cited by 8
Sampaziotis, F. (2018) · Science · doi:10.1126/science.aat0964 · Cited by 7
Cellular Systems Biology Applied to Preclinical Safety Testing: A Case Study of CellCiphrTMProfiling
Vernetti, L., Irwin, W., Giuliano, K. A., Gough, A., Johnston, K., & Taylor, D. L. (2008) · Drug Efficacy, Safety, and Biologics Discovery · doi:10.1002/9780470431818.ch3 · Cited by 6
Self-citationSynthetic Maturation of Multilineage Human Liver Organoids via Genetically Guided EngineeringPreprint
Velazquez, J. J., LeGraw, R., Moghadam, F., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.10.087445 · Cited by 4
Compound Attrition in Phase II/III
Alex, A., Harris, C., Keighley, W. W., & Smith, D. A. (2015) · doi:10.1002/9781118819586.ch4 · Cited by 2
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).
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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
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