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.
“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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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WITHDRAWN—a resource for withdrawn and discontinued drugs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 · see citing works
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 · see citing works
Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Hepatic stellate cells as key target in liver fibrosis
Higashi, T., Friedman, S. L., & Hoshida, Y. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.05.007 · Cited by 1,485 · see citing works
Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., et al. (2017) · Nature Medicine · doi:10.1038/nm.4438 · Cited by 1,471 · see citing works
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Microscale culture of human liver cells for drug development
Khetani, S. R., & Bhatia, S. N. (2008) · Nature Biotechnology · doi:10.1038/nbt1361 · Cited by 1,219 · see citing works
PDMS absorption of small molecules and consequences in microfluidic applications
Toepke, M. W., & Beebe, D. J. (2006) · Lab on a Chip · doi:10.1039/b612140c · Cited by 1,193 · see citing works
The integrative biology of type 2 diabetes
Roden, M., & Shulman, G. I. (2019) · Nature · doi:10.1038/s41586-019-1797-8 · Cited by 1,167 · see citing works
McPherson, S., Hardy, T., Henderson, E., Burt, A. D., Day, C. P., & Anstee, Q. M. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.11.034 · Cited by 1,059 · see citing works
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver
Halpern, K. B., Shenhav, R., Matcovitch-Natan, O., Tóth, B., Lemze, D., Golan, M., Massasa, E. E., Baydatch, S., Landen, S., Moor, A. E., et al. (2017) · Nature · doi:10.1038/nature21065 · Cited by 1,059 · see citing works
Liver sinusoidal endothelial cells: Physiology and role in liver diseases
Poisson, J., Lemoinne, S., Boulanger, C., Durand, F., Moreau, R., Valla, D., & Rautou, P.-E. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.07.009 · Cited by 1,047 · see citing works
Organs-on-chips: into the next decade
Low, L. A., Mummery, C., Berridge, B. R., Austin, C. P., & Tagle, D. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0079-3 · Cited by 1,029 · see citing works
Targeting hepatic macrophages to treat liver diseases
Tacke, F. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.02.026 · Cited by 1,003 · see citing works
Tilg, H., Moschen, A. R., & Roden, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.147 · Cited by 1,002 · see citing works
Maschmeyer, I., Lorenz, A. K., Schimek, K., Hasenberg, T., Ramme, A. P., Hübner, J., Lindner, M., Drewell, C., Bauer, S., Thomas, A., et al. (2015) · Lab on a Chip · doi:10.1039/c5lc00392j · Cited by 861 · see citing works
Three-Dimensional Cell Cultures in Drug Discovery and Development
Fang, Y., & Eglen, R. M. (2017) · SLAS Discovery · doi:10.1177/1087057117696795 · Cited by 849 · see citing works
Park, S. E., Georgescu, A., & Huh, D. (2019) · Science · doi:10.1126/science.aaw7894 · Cited by 847 · see citing works
Wang, G., McCain, M. L., Yang, L., He, A., Pasqualini, F. S., Agarwal, A., Yuan, H., Jiang, D., Zhang, D., Zangi, L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3545 · Cited by 837 · see citing works
Zhang, Y. S., Aleman, J., Shin, S. R., Kilic, T., Kim, D., Mousavi Shaegh, S. A., Massa, S., Riahi, R., Chae, S., Hu, N., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612906114 · Cited by 833 · see citing works
A decade of transcription factor-mediated reprogramming to pluripotency
Takahashi, K., & Yamanaka, S. (2016) · Nature reviews. Molecular cell biology · doi:10.1038/nrm.2016.8 · Cited by 815 · see citing works
Biological implications of polydimethylsiloxane-based microfluidic cell culture
Regehr, K. J., Domenech, M., Koepsel, J. T., Carver, K. C., Ellison-Zelski, S. J., Murphy, W. L., Schuler, L. A., Alarid, E. T., & Beebe, D. J. (2009) · Lab on a Chip · doi:10.1039/b903043c · Cited by 719 · see citing works
Three-dimensional organotypic culture: experimental models of mammalian biology and disease
Shamir, E. R., & Ewald, A. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3873 · Cited by 719 · see citing works
Phase II and Phase III attrition rates 2011–2012
Arrowsmith, J., & Miller, P. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4090 · Cited by 697 · cited 1× · see citing works
“The key characteristics of current HBL- MPS platforms include (1) the ability to experimentally combine, exclude and/or engineer the cell types included in a given study as well as to alter microenvironmental cues, such as matrix stiffness and biochemistry, to define their effect on ADMET and disease models (TableS 2,…”
BackgroundCurrent and future pharmacological therapies for NAFLD/NASH
Sumida, Y., & Yoneda, M. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1415-1 · Cited by 670 · see citing works
Organs-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development
Ronaldson-Bouchard, K., & Vunjak-Novakovic, G. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.02.011 · Cited by 657 · see citing works
Mittal, S., El-Serag, H. B., Sada, Y. H., Kanwal, F., Duan, Z., Temple, S., May, S. B., Kramer, J. R., Richardson, P. A., & Davila, J. A. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2015.07.019 · Cited by 648 · see citing works
Yi, H.-G., Jeong, Y. H., Kim, Y., Choi, Y.-J., Moon, H. E., Park, S. H., Kang, K. S., Bae, M., Jang, J., Youn, H., et al. (2019) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0363-x · Cited by 634 · see citing works
Organoids: A historical perspective of thinking in three dimensions
Simian, M., & Bissell, M. J. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610056 · Cited by 620 · see citing works
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 619 · see citing works
Noninvasive biomarkers in NAFLD and NASH — current progress and future promise
Wong, V. W., Adams, L. A., de Lédinghen, V., Wong, G. L., & Sookoian, S. C. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0014-9 · Cited by 617 · see citing works
Isabella, V. M., Ha, B. N., Castillo, M. J., Lubkowicz, D. J., Rowe, S. E., Millet, Y. A., Anderson, C. L., Li, N., Fisher, A. B., West, K. A., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4222 · Cited by 605 · see citing works
Hidvegi, T., Ewing, M., Hale, P. D., Dippold, C. S., Beckett, C. S., Kemp, C., Maurice, N. M., Mukherjee, A., Goldbach, C., Watkins, S. C., et al. (2010) · Science · doi:10.1126/science.1190354 · Cited by 604 · see citing works
Piscaglia, F., Svegliati‐Baroni, G., Barchetti, A., Pecorelli, A., Marinelli, S., Tiribelli, C., Bellentani, S., & on behalf of the HCC‐NAFLD Italian Study Group (2016) · Hepatology · doi:10.1002/hep.28368 · Cited by 604 · see citing works
Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team
Dyson, J., Jaques, B., Chattopadyhay, D., Lochan, R., Graham, J., Das, D., Aslam, T., Patanwala, I., Gaggar, S., Cole, M., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2013.08.011 · Cited by 603 · see citing works
Goldberg, D. S., Ditah, I. C., Saeian, K., Lalehzari, M., Aronsohn, A. I., Gorospe, E. C., & Charlton, M. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.003 · Cited by 601 · see citing works
<i>Ex Vivo</i> Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids
Jenkins, R. W., Aref, A. R., Lizotte, P. H., Ivanova, E., Stinson, S., Zhou, C. W., Bowden, M., Deng, J., Liu, H., Miao, D., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0833 · Cited by 594 · see citing works
Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids
Ouchi, R., Togo, S., Kimura, M., Shinozawa, T., Koido, M., Koike, H., Thompson, W., Karns, R. A., Mayhew, C. N., McGrath, P. S., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.007 · Cited by 537 · see citing works
Clinical and economic burden of adverse drug reactions
Sultana, J., Cutroneo, P. M., & Trifirò, G. (2013) · Journal of Pharmacology and Pharmacotherapeutics · doi:10.4103/0976-500x.120957 · Cited by 530 · see citing works
Past, present and future perspectives in nonalcoholic fatty liver disease
Sanyal, A. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0144-8 · Cited by 522 · see citing works
Reproducing human and cross-species drug toxicities using a liver-chip
Jang, K.-J., Otieno, M. A., Ronxhi, J., Lim, H.-K., Ewart, L., Kodella, K. R., Petropolis, D. B., Kulkarni, G., Rubins, J. E., Conegliano, D., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aax5516 · Cited by 511 · see citing works
Herland, A., Maoz, B. M., Das, D., Somayaji, M. R., Prantil‐Baun, R., Novak, R., Cronce, M. J., Huffstater, T. M., Jeanty, S. S. F., Ingram, M., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-019-0498-9 · Cited by 505 · see citing works
Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies
Edington, C. D., Chen, W. L. K., Geishecker, E., Kassis, T., Soenksen, L. R., Bhushan, B. M., Freake, D., Kirschner, J., Maass, C., Tsamandouras, N., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-22749-0 · Cited by 487 · see citing works
Adaptive design methods in clinical trials–a review
Chow, S.-C., & Chang, M. (2008) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-3-11 · Cited by 482 · see citing works
Perfused multiwell plate for 3D liver tissue engineering
Domanský, K., Inman, W., Serdy, J., Dash, A., Lim, M. H. M., & Griffith, L. G. (2009) · Lab on a Chip · doi:10.1039/b913221j · Cited by 446 · see citing works
Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs
Oleaga, C., Bernabini, C., Smith, A. S. T., Srinivasan, B., Jackson, M., McLamb, W., Platt, V., Bridges, R., Cai, Y., Santhanam, N., et al. (2016) · Scientific Reports · doi:10.1038/srep20030 · Cited by 442 · see citing works
Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies
Musso, G., Cassader, M., & Gambino, R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.3 · Cited by 415 · see citing works
The hope and the hype of organoid research
Huch, M., Knoblich, J. A., Lutolf, M. P., & Martinez-Arias, A. (2017) · Development · doi:10.1242/dev.150201 · Cited by 409 · see citing works
Younossi, Z. M., Marchesini, G., Cortez‐Pinto, H., & Petta, S. (2018) · Transplantation · doi:10.1097/tp.0000000000002484 · Cited by 405 · see citing works
Hepatocytes direct the formation of a pro-metastatic niche in the liver
Lee, J. W., Stone, M. L., Porrett, P. M., Thomas, S. K., Komar, C. A., Li, J. H., Delman, D., Graham, K., Gladney, W. L., Hua, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1004-y · Cited by 402 · see citing works
Sampaziotis, F., de Brito, M. C., Madrigal, P., Bertero, A., Saeb‐Parsy, K., Soares, F. A. C., Schrumpf, E., Melum, E., Karlsen, T. H., Bradley, J. A., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3275 · Cited by 398 · see citing works
The Reprogramming of Tumor Stroma by HSF1 Is a Potent Enabler of Malignancy
Scherz-Shouval, R., Santagata, S., Mendillo, M. L., Sholl, L. M., Ben-Aharon, I., Beck, A. H., Dias-Santagata, D., Koeva, M., Stemmer, S. M., Whitesell, L., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.045 · Cited by 386 · see citing works
Nguyen, D. G., Funk, J., Robbins, J. B., Crogan‐Grundy, C., Presnell, S. C., Singer, T., & Roth, A. B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158674 · Cited by 385 · see citing works
Younossi, Z. M., Loomba, R. S., Rinella, M. E., Bugianesi, E., Marchesini, G., Neuschwander‐Tetri, B. A., Serfaty, L., Negro, F., Caldwell, S. H., Ratziu, V., et al. (2017) · Hepatology · doi:10.1002/hep.29724 · Cited by 382 · see citing works
Gribkoff, V. K., & Kaczmarek, L. K. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.021 · Cited by 379 · see citing works
Disease modelling in human organoids
Lancaster, M. A., & Huch, M. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039347 · Cited by 379 · see citing works
Bavli, D., Prill, S., Tsur, E. E., Levy, G., Cohen, M., Vinken, M., Vanfleteren, J., Jaeger, M. S., & Nahmias, Y. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522556113 · Cited by 366 · see citing works
Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease
Hammoutene, A., & Rautou, P.-E. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.02.012 · Cited by 364 · see citing works
Moore, T. J., Zhang, H., Anderson, G., & Alexander, G. C. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2018.3931 · Cited by 356 · see citing works
Liver organoids: from basic research to therapeutic applications
Prior, N., Inacio, P., & Huch, M. (2019) · Gut · doi:10.1136/gutjnl-2019-319256 · Cited by 356 · see citing works
Utility of spherical human liver microtissues for prediction of clinical drug-induced liver injury
Proctor, W. R., Foster, A. J., Vogt, J., Summers, C., Middleton, B., Pilling, M. A., Shienson, D., Kijanska, M., Ströbel, S., Kelm, J. M., et al. (2017) · Archives of Toxicology · doi:10.1007/s00204-017-2002-1 · Cited by 328 · see citing works
Greene, C. M., Marciniak, S. J., Teckman, J. H., Ferrarotti, I., Brantly, M., Lomas, D. A., Stoller, J. K., & McElvaney, N. G. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.51 · Cited by 326 · see citing works
Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary
Koike, H., Iwasawa, K., Ouchi, R., Maezawa, M., Giesbrecht, K., Saiki, N., Ferguson, A., Kimura, M., Thompson, W. L., Wells, J. M., et al. (2019) · Nature · doi:10.1038/s41586-019-1598-0 · Cited by 325 · see citing works
Shirure, V. S., Bi, Y., Curtis, M. B., Lezia, A., Goedegebuure, M. M., Goedegebuure, S. P., Aft, R., Fields, R. C., & George, S. C. (2018) · Lab on a Chip · doi:10.1039/c8lc00596f · Cited by 316 · see citing works
Organ-on-a-chip platforms: a convergence of advanced materials, cells, and microscale technologies
Ahadian, S., Civitarese, R., Bannerman, D., Mohammadi, M. H., Lu, R., Wang, E., Davenport‐Huyer, L., Lai, B., Zhang, B., Zhao, Y., et al. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201700506 · Cited by 315 · see citing works
Scaling and systems biology for integrating multiple organs-on-a-chip
Wikswo, J. P., Curtis, E. L., Eagleton, Z. E., Evans, B. C., Kole, A., Hofmeister, L. H., & Matloff, W. J. (2013) · Lab on a Chip · doi:10.1039/c3lc50243k · Cited by 310 · see citing works
Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology
Eslam, M., & George, J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0212-0 · Cited by 310 · see citing works
Mechanisms of Immune-Mediated Liver Injury
Adams, D., Ju, C., Ramaiah, S. K., Uetrecht, J., & Jaeschke, H. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq009 · Cited by 297 · see citing works
Sampaziotis, F., Justin, A. W., Tysoe, O. C., Sawiak, S., Godfrey, E. M., Upponi, S. S., Gieseck, R. L., de Brito, M. C., Berntsen, N. L., Gómez-Vázquez, M. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4360 · Cited by 296 · see citing works
Multi-lineage human iPSC-derived platforms for disease modeling and drug discovery
Sharma, A., Sances, S., Workman, M. J., & Svendsen, C. N. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.02.011 · Cited by 296 · see citing works
Marx, U. (2016) · ALTEX · doi:10.14573/altex.1603161 · Cited by 295 · see citing works
Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease
Ramli, M. N. B., Lim, Y. S., Koe, C. T., Demircioglu, D., Tng, W., Gonzales, K. A. U., Tan, C. P., Szczerbinska, I., Liang, H., Soe, E. L., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.06.010 · Cited by 278 · see citing works
Vernetti, L. A., Gough, A., Baetz, N. W., Blutt, S. E., Broughman, J. R., Brown, J. A., Foulke-Abel, J. D., Hasan, N. M., In, J., Kelly, E. J., et al. (2017) · Scientific Reports · doi:10.1038/srep42296 · Cited by 274 · see citing works
Self-citationBauer, S., Wennberg Huldt, C., Kanebratt, K. P., Durieux, I., Gunne, D., Andersson, S., Ewart, L., Haynes, W. G., Maschmeyer, I., Winter, A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-14815-w · Cited by 272 · see citing works
Aref, A. R., Campisi, M., Ivanova, E., Portell, A., Larios, D., Piel, B. P., Mathur, N., Zhou, C., Coakley, R. V., Bartels, A., et al. (2018) · Lab on a Chip · doi:10.1039/c8lc00322j · Cited by 265 · see citing works
Synergistic Engineering: Organoids Meet Organs-on-a-Chip
Takebe, T., Zhang, B., & Radisic, M. (2017) · Cell Stem Cell · doi:10.1016/j.stem.2017.08.016 · Cited by 258 · see citing works
Recent Advances in Body-on-a-Chip Systems
Sung, J. H., Wang, Y. I., Narasimhan Sriram, N., Jackson, M., Long, C., Hickman, J. J., & Shuler, M. L. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05293 · Cited by 258 · see citing works
Genetics of Phenylketonuria: Then and Now
Blau, N. (2016) · Human Mutation · doi:10.1002/humu.22980 · Cited by 244 · see citing works
Human hepatic organoids for the analysis of human genetic diseases
Guan, Y., Xu, D., Garfin, P. M., Ehmer, U., Hurwitz, M., Enns, G., Michie, S., Wu, M., Zheng, M., Nishimura, T., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.94954 · Cited by 243 · see citing works
Design and demonstration of a pumpless 14 compartment microphysiological system
Miller, P. G., & Shuler, M. L. (2016) · Biotechnology and Bioengineering · doi:10.1002/bit.25989 · Cited by 235 · see citing works
Coll, M., Perea, L., Boon, R., Leite, S. B., Vallverdú, J., Mannaerts, I., Smout, A., El Taghdouini, A., Blaya, D., Rodrigo-Torres, D., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.05.027 · Cited by 233 · see citing works
A human liver microphysiology platform for investigating physiology, drug safety, and disease models
Vernetti, L. A., Senutovitch, N., Boltz, R. C., DeBiasio, R., Shun, T. Y., Gough, A., & Taylor, D. L. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215592121 · Cited by 230 · see citing works
Self-citationEstablishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma
Saito, Y., Muramatsu, T., Kanai, Y., Ojima, H., Sukeda, A., Hiraoka, N., Arai, E., Sugiyama, Y., Matsuzaki, J., Uchida, R., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.088 · Cited by 227 · see citing works
Drug Metabolism in Adult Rat Hepatocytes in Primary Monolayer Culture
Guzelian, P. S., Bissell, D. M., & Meyer, U. (1977) · Gastroenterology · doi:10.1016/s0016-5085(77)80017-6 · Cited by 226 · see citing works
Esch, M. B., Ueno, H., Applegate, D. R., & Shuler, M. L. (2016) · Lab on a Chip · doi:10.1039/c6lc00461j · Cited by 223 · see citing works
Tsamandouras, N., Chen, W. L. K., Edington, C. D., Stokes, C. L., Griffith, L. G., & Cirit, M. (2017) · The AAPS Journal · doi:10.1208/s12248-017-0122-4 · Cited by 222 · see citing works
Wang, Y., Wang, H., Deng, P., Chen, W., Guo, Y., Tao, T., & Qin, J. (2018) · Lab on a Chip · doi:10.1039/c8lc00869h · Cited by 222 · see citing works
A microfluidic hepatic coculture platform for cell-based drug metabolism studies
Novik, E., Maguire, T. J., Chao, P., Cheng, K.-C., & Yarmush, M. L. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.11.010 · Cited by 213 · see citing works
Beckwitt, C. H., Clark, A. M., Wheeler, S., Taylor, D. L., Stolz, D. B., Griffith, L. G., & Wells, A. H. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.12.023 · Cited by 211 · see citing works
Self-citationHepatic fibrosis: It is time to go with hepatic stellate cell-specific therapeutic targets
Ezhilarasan, D., Sokal, E., & Najimi, M. (2018) · Hepatobiliary & Pancreatic Diseases International · doi:10.1016/j.hbpd.2018.04.003 · Cited by 204 · see citing works
Drug‐induced liver injury: Advances in mechanistic understanding that will inform risk management
Mosedale, M., & Watkins, P. B. (2016) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.564 · Cited by 203 · see citing works
Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system
Wang, Y., Wang, L., Guo, Y., Zhu, Y., & Qin, J. (2018) · RSC Advances · doi:10.1039/c7ra11714k · Cited by 201 · see citing works
Brown, J. A., Codreanu, S. G., Shi, M., Sherrod, S. D., Markov, D. A., Neely, M. D., Britt, C. M., Hoilett, O. S., Reiserer, R. S., Samson, P. C., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0760-y · Cited by 200 · see citing works
Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics
McAleer, C. W., Long, C. J., Elbrecht, D., Sasserath, T., Bridges, L. R., Rumsey, J. W., Martin, C., Schnepper, M., Wang, Y., Schuler, F., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav1386 · Cited by 199 · see citing works
Avila, A. M., Bebenek, I., Bonzo, J. A., Bourcier, T., Bruno, K. L. D., Carlson, D. B., Dubinion, J. H., Elayan, I., Harrouk, W. A., Lee, S., et al. (2020) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2020.104662 · Cited by 197 · see citing works
Berger, D. R., Ware, B. R., Davidson, M. D., Allsup, S. R., & Khetani, S. R. (2014) · Hepatology · doi:10.1002/hep.27621 · Cited by 194 · see citing works
Hoang, S. A., Oseini, A. M., Feaver, R. E., Cole, B. K., Asgharpour, A., Vincent, R. J., Siddiqui, M. S., Lawson, M. J., Day, N., Taylor, J. M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-48746-5 · Cited by 191 · see citing works
Microfluidic titer plate for stratified 3D cell culture
Trietsch, S. J., Israëls, G. D., Joore, J., Hankemeier, T., & Vulto, P. (2013) · Lab on a Chip · doi:10.1039/c3lc50210d · Cited by 189 · see citing works
Vernetti, L. A., Gough, A., Baetz, N. W., Blutt, S. E., Broughman, J. R., Brown, J. A., Foulke-Abel, J. D., Hasan, N. M., In, J., Kelly, E. J., et al. (2017) · Scientific Reports · doi:10.1038/srep44517 · Cited by 189 · see citing works
Self-citationDisease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells
Ho, B. X., Pek, N. M. Q., & Soh, B.-S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040936 · Cited by 181 · see citing works
Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems
Wikswo, J. P., Block, F. E., Cliffel, D. E., Goodwin, C. R., Marasco, C. C., Markov, D. A., McLean, D. L., MCLEAN, J. A. J., McKenzie, J. R., Reiserer, R. S., et al. (2013) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2013.2244891 · Cited by 176 · see citing works
Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk
Chen, W. L. K., Edington, C., Suter, E., Yu, J., Velazquez, J. J., Velazquez, J. G., Shockley, M., Large, E. M., Venkataramanan, R., Hughes, D. J., et al. (2017) · Biotechnology and Bioengineering · doi:10.1002/bit.26370 · Cited by 171 · see citing works
Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges
Wang, Y. I., Carmona, C., Hickman, J. J., & Shuler, M. L. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201701000 · Cited by 168 · see citing works
Ma, L.-D., Wang, Y., Wang, J., Wu, J., Meng, X., Hu, P., Mu, X., Liang, Q., & Luo, G. (2018) · Lab on a Chip · doi:10.1039/c8lc00333e · Cited by 167 · see citing works
An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells
Koui, Y., Kido, T., Ito, T., Oyama, H., Chen, S.-W., Katou, Y., Shirahige, K., & Miyajima, A. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.06.010 · Cited by 163 · see citing works
Chao, P., Maguire, T. J., Novik, E., Cheng, K.-C., & Yarmush, M. L. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2009.05.013 · Cited by 161 · see citing works
Liver Sinusoidal Endothelial Cell: An Update
Maretti-Mira, A. C., & DeLeve, L. D. (2017) · Seminars in Liver Disease · doi:10.1055/s-0037-1617455 · Cited by 161 · see citing works
Guye, P., Ebrahimkhani, M. R., Kipniss, N. H., Velazquez, J. J., Schoenfeld, E., Kiani, S., Griffith, L. G., & Weiss, R. (2016) · Nature Communications · doi:10.1038/ncomms10243 · Cited by 155 · see citing works
Self-citationDevelopment of an in vitro human liver system for interrogating nonalcoholic steatohepatitis
Feaver, R. E., Cole, B. K., Lawson, M. J., Hoang, S. A., Marukian, S., Blackman, B. R., Figler, R. A., Sanyal, A. J., Wamhoff, B. R., & Dash, A. (2016) · JCI Insight · doi:10.1172/jci.insight.90954 · Cited by 153 · see citing works
Baudy, A. R., Otieno, M. A., Hewitt, P., Gan, J., Roth, A., Keller, D., Sura, R., Van Vleet, T. R., & Proctor, W. R. (2020) · Lab on a Chip · doi:10.1039/c9lc00768g · Cited by 150 · see citing works
Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease
Kostrzewski, T. M., Cornforth, T. V., Snow, S., Ouro-Gnao, L., Rowe, C., Large, E. M., & Hughes, D. J. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i2.204 · Cited by 149 · see citing works
Norona, L. M., Nguyen, D. G., Gerber, D. A., Presnell, S. C., & LeCluyse, E. L. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw169 · Cited by 145 · see citing works
Monogenic diseases that can be cured by liver transplantation
FAGIUOLI, S., Daina, E., D’Antiga, L., Colledan, M., & Remuzzi, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.04.004 · Cited by 144 · see citing works
Kizawa, H., Nagao, E., Shimamura, M., Zhang, G., & Torii, H. (2017) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2017.04.004 · Cited by 143 · see citing works
Maruyama, M., Kobayashi, N., Westerman, K. A., Sakaguchi, M., Allain, J.-É., Totsugawa, T., Okitsu, T., Fukazawa, T., Weber, A., Stolz, D. B., et al. (2004) · Transplantation · doi:10.1097/01.tp.0000110292.73873.25 · Cited by 143 · see citing works
Lee-Montiel, F. T., George, S. M., Gough, A., Sharma, A. D., Wu, J., DeBiasio, R., Vernetti, L. A., & Taylor, D. L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217703978 · Cited by 141 · see citing works
Self-citationTissue chips – innovative tools for drug development and disease modeling
Low, L. A., & Tagle, D. A. (2017) · Lab on a Chip · doi:10.1039/c7lc00462a · Cited by 141 · see citing works
Li, X., George, S. M., Vernetti, L. A., Gough, A., & Taylor, D. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00418h · Cited by 138 · see citing works
Self-citationSundaram, V., & Björnsson, E. S. (2017) · Hepatology Communications · doi:10.1002/hep4.1088 · Cited by 138 · see citing works
Multi-Organs-on-Chips: Towards Long-Term Biomedical Investigations
Zhao, Y., Kankala, R. K., Wang, S., & Chen, A. (2019) · Molecules · doi:10.3390/molecules24040675 · Cited by 136 · see citing works
Sung, J. H., Srinivasan, B., Esch, M. B., McLamb, W., Bernabini, C., Shuler, M. L., & Hickman, J. J. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214529397 · Cited by 132 · see citing works
Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Mikolašević, I., Filipec-Kanižaj, T., Mijić, M., Jakopčić, I., Milić, S., Hrstić, I., Sobočan, N., Štimac, D., & Burra, P. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i14.1491 · Cited by 131 · see citing works
Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery
Ewart, L. C., Dehne, E., Fabre, K. M., Gibbs, S., Hickman, J. J., Hornberg, E., Ingelman‐Sundberg, M., Jang, K., Jones, D. R., Lauschke, V. M., et al. (2017) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010617-052722 · Cited by 130 · see citing works
Challenges and Opportunities in the Design of Liver-on-Chip Microdevices
Ehrlich, A., Duche, D., Ouedraogo, G., & Nahmias, Y. (2019) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-060418-052305 · Cited by 125 · see citing works
Tsamandouras, N., Kostrzewski, T. M., Stokes, C. L., Griffith, L. G., Hughes, D. J., & Cirit, M. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.237495 · Cited by 119 · see citing works
Foster, A. J., Chouhan, B., Regan, S. L., Rollison, H., Amberntsson, S., Andersson, L. C., Srivastava, A., Darnell, M., Cairns, J., Lazic, S. E., et al. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02427-4 · Cited by 117 · see citing works
Sampaziotis, F., de Brito, M. C., Geti, I., Bertero, A., Hannan, N. R. F., & Vallier, L. (2017) · Nature Protocols · doi:10.1038/nprot.2017.011 · Cited by 115 · see citing works
Clinical and Economic Burden of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Younossi, Z. M., Henry, L. L., Bush, H., & Mishra, A. (2017) · Clinics in Liver Disease · doi:10.1016/j.cld.2017.08.001 · Cited by 111 · see citing works
Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro
Dash, A., Simmers, M. B., Deering, T. G., Berry, D. J., Feaver, R. E., Hastings, N. E., Pruett, T. L., LeCluyse, E. L., Blackman, B. R., & Wamhoff, B. R. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00331.2012 · Cited by 108 · see citing works
Generation of mature kupffer cells from human induced pluripotent stem cells
Tasnim, F., Xing, J., Huang, X., Mo, S., Wei, X., Tan, M., & Yu, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.11.016 · Cited by 107 · see citing works
Tabibian, J. H., Trussoni, C. E., O’Hara, S. P., Splinter, P. L., Heimbach, J. K., & LaRusso, N. F. (2014) · Laboratory Investigation · doi:10.1038/labinvest.2014.94 · Cited by 105 · see citing works
A Toxicology for the 21st Century—Mapping the Road Ahead
Härtung, T. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp059 · Cited by 105 · see citing works
Spontaneous dormancy of metastatic breast cancer cells in an all human liver microphysiologic system
Wheeler, S., Clark, A. M., Taylor, D. P., Young, C. L., Pillai, V. C., Stolz, D. B., Venkataramanan, R., Lauffenburger, D. A., Griffith, L. G., & Wells, A. H. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.533 · Cited by 102 · see citing works
Self-citationStatins attenuate outgrowth of breast cancer metastases
Beckwitt, C. H., Clark, A. M., Ma, B., Whaley, D., Oltvai, Z. N., & Wells, A. H. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0267-7 · Cited by 102 · see citing works
Jardim, D. L. F., Groves, E. S., Breitfeld, P. P., & Kurzrock, R. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.10.009 · Cited by 101 · see citing works
de l’Hortet, A. C., Takeishi, K., Guzman‐Lepe, J., Morita, K., Achreja, A., Popovic, B., Wang, Y., Handa, K., Mittal, A., Meurs, N., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.017 · Cited by 101 · see citing works
Prestigiacomo, V., Weston, A. A., Messner, S., Lampart, F. L., & Suter‐Dick, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179995 · Cited by 100 · see citing works
On-chip three-dimensional cell culture in phaseguides improves hepatocyte functions in vitro
Jang, M., Neužil, P., Volk, T. J., Manz, A., & Kleber, A. (2015) · Biomicrofluidics · doi:10.1063/1.4922863 · Cited by 98 · see citing works
McAleer, C. W., Pointon, A., Long, C. J., Brighton, R. L., Wilkin, B. D., Bridges, L. R., Sriram, N. N., Fabre, K. M., McDougall, R., Muse, V., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45656-4 · Cited by 97 · see citing works
Organs-on-chip monitoring: sensors and other strategies
Kilic, T., Navaee, F., Stradolini, F., Renaud, P., & Carrara, S. (2018) · Microphysiological Systems · doi:10.21037/mps.2018.01.01 · Cited by 96 · see citing works
ESTABLISHMENT OF AN IMMORTALIZED HUMAN-LIVER ENDOTHELIAL CELL LINE WITH SV40T AND hTERT
Matsumura, T., Takesue, M., Westerman, K. A., Okitsu, T., Sakaguchi, M., Fukazawa, T., Totsugawa, T., Noguchi, H., Yamamoto, S., Stolz, D. B., et al. (2004) · Transplantation · doi:10.1097/01.tp.0000124286.82961.7e · Cited by 95 · see citing works
Long, T. J., Cosgrove, P. A., Dunn, R. T., Stolz, D. B., Hamadeh, H. K., Afshari, C. A., McBride, H. J., & Griffith, L. G. (2016) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.071456 · Cited by 94 · see citing works
Bricks, T., Paullier, P., Legendre, A., Fleury, M., Zeller, P., Merlier, F., Anton, P. M., & Leclerc, É. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2014.02.005 · Cited by 91 · see citing works
Tafaleng, E. N., Chakraborty, S., Han, B., Hale, P. D., Wu, W., Soto–Gutiérrez, A., Feghali‐Bostwick, C. A., Wilson, A. A., Kotton, D. N., Nagaya, M., et al. (2015) · Hepatology · doi:10.1002/hep.27753 · Cited by 91 · see citing works
Soto–Gutiérrez, A., Gough, A., Vernetti, L. A., Taylor, D. L., & Monga, S. P. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217707731 · Cited by 91 · see citing works
Self-citationNavigating tissue chips from development to dissemination: A pharmaceutical industry perspective
Ewart, L. C., Fabre, K. M., Chakilam, A. R., Dragan, Y. P., Duignan, D. B., Eswaraka, J., Gan, J., Guzzie‐Peck, P., Otieno, M. A., Jeong, C. G., et al. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217715441 · Cited by 89 · see citing works
Chemical-PDMS binding kinetics and implications for bioavailability in microfluidic devices
Auner, A. W., Tasneem, K. M., Markov, D. A., McCawley, L. J., & Hutson, M. S. (2019) · Lab on a Chip · doi:10.1039/c8lc00796a · Cited by 87 · see citing works
Zhou, Y., Shen, J. X., & Lauschke, V. M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01093 · Cited by 85 · see citing works
Induced Pluripotent Stem Cell–Derived Endothelial Cells
Jang, S. K., de l’Hortet, A. C., & Soto–Gutiérrez, A. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.12.004 · Cited by 85 · see citing works
Polygenic architecture informs potential vulnerability to drug-induced liver injury
Koido, M., Kawakami, E., Fukumura, J., Noguchi, Y., Ohori, M., Nio, Y., Nicoletti, P., Aithal, G. P., Daly, A. K., Watkins, P. B., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1023-0 · Cited by 84 · see citing works
Human adult hepatocytes in primary monolayer culture
Grant, M. H., Burke, M. D., HAWKSWORTH, G. M., et al. (1987) · Biochemical Pharmacology · doi:10.1016/0006-2952(87)90596-x · Cited by 84 · see citing works
Substrate stiffness regulates primary hepatocyte functions
Natarajan, V., Berglund, E. J., Chen, D. X., & Kidambi, S. (2015) · RSC Advances · doi:10.1039/c5ra15208a · Cited by 84 · see citing works
Bhushan, A., Senutovitch, N., Bale, S. S., McCarty, W. J., Hegde, M., Jindal, R., Golberg, I., Usta, O. B., Yarmush, M. L., Vernetti, L. A., et al. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt377 · Cited by 83 · see citing works
Self-citationVunjak‐Novakovic, G., Bhatia, S. N., Chen, C. S., & Hirschi, K. K. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt369 · Cited by 80 · see citing works
Norona, L. M., Nguyen, D. G., Gerber, D. A., Presnell, S. C., Mosedale, M., & Watkins, P. B. (2019) · PLoS ONE · doi:10.1371/journal.pone.0208958 · Cited by 79 · see citing works
Stoller, J. K. (2004) · Thorax · doi:10.1136/thorax.2003.017517 · Cited by 79 · see citing works
A Bile Duct‐on‐a‐Chip With Organ‐Level Functions
Du, Y. M., Khandekar, G., Llewellyn, J., Polacheck, W. J., Chen, C. S., & Wells, R. G. (2019) · Hepatology · doi:10.1002/hep.30918 · Cited by 79 · see citing works
Tan, K. Y. S., Keegan, P. M., Rogers, M. T., Lu, M., Gosset, J. R., Charest, J. L., & Bale, S. S. (2019) · Lab on a Chip · doi:10.1039/c8lc01262h · Cited by 78 · see citing works
Watson, D. E., Hunziker, R., & Wikswo, J. P. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217732765 · Cited by 78 · see citing works
Hazari, Y., Bashir, A., Habib, M., Bashir, S., Habib, H., Qasim, M. A., Shah, N. N., Haq, E., Teckman, J. H., & Fazili, K. M. (2017) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2017.03.001 · Cited by 77 · see citing works
A Microphysiological System for Studying Nonalcoholic Steatohepatitis
Kostrzewski, T., Maraver, P., Ouro‐Gnao, L., Levi, A., Snow, S., Miedzik, A., Rombouts, K., & Hughes, D. (2020) · Hepatology Communications · doi:10.1002/hep4.1450 · Cited by 77 · see citing works
In vitro metabolic zonation through oxygen gradient on a chip
Tonon, F., Giobbe, G. G., Zambon, A., Luni, C., Gagliano, O., Floreani, A., Grassi, G., & Elvassore, N. (2019) · Scientific Reports · doi:10.1038/s41598-019-49412-6 · Cited by 76 · see citing works
Parasrampuria, D. A., Benet, L. Z., & Sharma, A. (2018) · The AAPS Journal · doi:10.1208/s12248-018-0204-y · Cited by 76 · see citing works
Engineering microphysiological immune system responses on chips
Miller, C. P., Shin, W., Ahn, E. H., Kim, H. J., & Kim, D.-H. (2020) · Trends in biotechnology · doi:10.1016/j.tibtech.2020.01.003 · Cited by 74 · see citing works
Human Microphysiological Systems and Organoids as in Vitro Models for Toxicological Studies
Truskey, G. A. (2018) · Frontiers in Public Health · doi:10.3389/fpubh.2018.00185 · Cited by 72 · see citing works
Maximizing the impact of microphysiological systems with in vitro – in vivo translation
Cirit, M., & Stokes, C. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00039e · Cited by 70 · see citing works
Li, G., Huang, K., Nikolic, D. S., & van Breemen, R. B. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.065987 · Cited by 70 · see citing works
Intercellular Communication between Hepatic Cells in Liver Diseases
Sato, K., Kennedy, L. L., Liangpunsakul, S., Kusumanchi, P., Yang, Z., Meng, F., Glaser, S. S., Francis, H., & Alpini, G. D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092180 · Cited by 68 · see citing works
Turner, A. M., Stolk, J., Bals, R., Lickliter, J. D., Hamilton, J., Christianson, D. R., Given, B. D., Burdon, J. G., Loomba, R., Stoller, J. K., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.03.012 · Cited by 67 · see citing works
Prill, S., Bavli, D., Levy, G., Tsur, E. E., Schmälzlin, E., Jaeger, M. S., Schwarz, M., Duschl, C., Cohen, M., & Nahmias, Y. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1537-2 · Cited by 66 · see citing works
Davidson, M. D., Kukla, D. A., & Khetani, S. R. (2017) · Integrative Biology · doi:10.1039/c7ib00027h · Cited by 66 · see citing works
Roussel, R., Steg, P. G., Mohammedi, K., Marre, M., & Potier, L. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13033 · Cited by 66 · see citing works
Clinical and biochemical footprints of inherited metabolic diseases. II. Metabolic liver diseases
Ferreira, C. R., Cassiman, D. M., & Blau, N. (2019) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2019.04.002 · Cited by 65 · see citing works
Synthetic developmental biology: build and control multicellular systems
Ebrahimkhani, M. R., & Ebisuya, M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.04.006 · Cited by 63 · see citing works
Self-citationA microphysiological system model of therapy for liver micrometastases
Clark, A. M., Wheeler, S., Taylor, D. P., Pillai, V. C., Young, C. L., Prantil‐Baun, R., Nguyen, T., Stolz, D. B., Borenstein, J. T., Lauffenburger, D. A., et al. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214532596 · Cited by 62 · see citing works
Self-citationChoudhury, Y., Toh, Y., Xing, J., Qu, Y., Poh, J., Li, H., Tan, H. S., Kanesvaran, R., Yu, H., & Tan, M. (2017) · Scientific Reports · doi:10.1038/srep41238 · Cited by 61 · see citing works
Engineering multicellular systems: Using synthetic biology to control tissue self-organization
Johnson, M. B., March, A. R., & Morsut, L. (2017) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2017.10.008 · Cited by 61 · see citing works
Advances in Engineered Human Liver Platforms for Drug Metabolism Studies
Underhill, G. H., & Khetani, S. R. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.083295 · Cited by 61 · see citing works
Clark, A. M., Kumar, M. P., Wheeler, S., Young, C. L., Venkataramanan, R., Stolz, D. B., Griffith, L. G., Lauffenburger, D. A., & Wells, A. H. (2018) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra117.000370 · Cited by 56 · see citing works
Li, J., Zhao, Y.-R., & Tian, Z. (2019) · World Journal of Hepatology · doi:10.4254/wjh.v11.i5.412 · Cited by 55 · see citing works
Assessing the therapeutic potential of lab-made hepatocytes
Rezvani, M., Grimm, A. A., & Willenbring, H. (2016) · Hepatology · doi:10.1002/hep.28569 · Cited by 54 · see citing works
Tagle, D. A. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.09.007 · Cited by 54 · see citing works
Human-based systems: Mechanistic NASH modelling just around the corner?
Boeckmans, J., Natale, A., Buyl, K., Rogiers, V., Kock, J. D., Vanhaecke, T., & Rodrigues, R. M. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.06.029 · Cited by 53 · see citing works
Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease
Ghouse, R., Chu, A. S., Wang, Y., & Perlmutter, D. H. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.014092 · Cited by 51 · see citing works
Emerging Role of Organ‐on‐a‐Chip Technologies in Quantitative Clinical Pharmacology Evaluation
Isoherranen, N., Madabushi, R., & Huang, S. M. (2019) · Clinical and Translational Science · doi:10.1111/cts.12627 · Cited by 50 · see citing works
Colnot, S., & Perret, C. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-7107-4_2 · Cited by 50 · see citing works
Evolution of Experimental Models of the Liver to Predict Human Drug Hepatotoxicity and Efficacy
Vernetti, L. A., Vogt, A., Gough, A., & Taylor, D. L. (2016) · Clinics in Liver Disease · doi:10.1016/j.cld.2016.08.013 · Cited by 50 · see citing works
Self-citationShen, J. X., Youhanna, S. C., Shafagh, R. Z., Kele, J., & Lauschke, V. M. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.9b00245 · Cited by 48 · see citing works
Stern, A. M., Schurdak, M. E., Bahar, İ., Berg, J. M., & Taylor, D. L. (2016) · SLAS DISCOVERY · doi:10.1177/1087057116635818 · Cited by 47 · see citing works
Self-citationWang, X., Cirit, M., Wishnok, J. S., Griffith, L. G., & Tannenbaum, S. R. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b02224 · Cited by 47 · see citing works
Boeri, L., Izzo, L., Sardelli, L., Tunesi, M., Albani, D., & Giordano, C. (2019) · Bioengineering · doi:10.3390/bioengineering6040091 · Cited by 45 · see citing works
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 45 · see citing works
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 44 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 5
- [1]Alex A, Harris CJ, Keighley WW & Smith DA In Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward (eds Alex A, Harris CJ & Smith DA) 106– 127 (Wiley, 2015).
- [17]Vernetti L in Drug Efficacy, Safety, and Biologics Discovery: Emerging Technologies and Tools (eds Ekins S & Xu JJ) Ch. 3, 53– 73 (Wiley & Sons, 2009).
- [30]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).
- [105]Colnot S & Perret C in Molecular Pathology of Liver Diseases (ed. Satdarshan S & Monga P) 7– 16 (Springer, 2011).
- [186]Bergenthal LM, Shun TY, Vernetti L, Taylor DL & Gough AH The Microphysiology Systems Database http://mps.csb.pitt.edu (2018). PMC5119471 28781990
Cited by
Sorted by citations
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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 · see citing works
Constructing biomimetic liver models through biomaterials and vasculature engineering
Lv, W., Zhou, H., Aazmi, A., Yu, M., Xu, X., Yang, H., Huang, Y. Y. S., & Ma, L. (2022) · Regenerative Biomaterials · doi:10.1093/rb/rbac079 · Cited by 45 · see citing works
Liver organoids: established tools for disease modeling and drug development
Sun, X.-C., Kong, D.-F., Zhao, J., Faber, K. N., Xia, Q., & He, K. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000105 · Cited by 37 · see citing works
Biomimetic hepatic lobules from three-dimensional imprinted cell sheets
Wang, J., Huang, D., Chen, H., & Zhao, Y. (2024) · Science Bulletin · doi:10.1016/j.scib.2024.02.030 · Cited by 37 · see citing works
Developing Liver Microphysiological Systems for Biomedical Applications
Wang, J., Wu, X., Zhao, J., Ren, H., & Zhao, Y. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202302217 · Cited by 27 · see citing works
Biomimetic Vascularized iPSC‐Hepatocyte Spheroids for Liver Regeneration
Wang, J., Huang, D., Ren, H., & Zhao, Y. (2025) · Advanced Science · doi:10.1002/advs.202405662 · Cited by 13 · see citing works
- 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
- 244
- 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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