Cited by 1223D Printing in Biomedical ResearchTissue Engineering and Regenerative MedicineDrug-Induced Hepatotoxicity and Protection

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 access

Gough, Albert, Soto-Gutierrez, Alejandro, Vernetti, Lawrence, Ebrahimkhani, Mo R., Stern, Andrew M., Taylor, D. Lansing·2021·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/s41575-020-00386-1PMC PMC9106093

Open this paper in CoChat — free account

Abstract

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.

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

Crossref · 10.1038/s41575-020-00386-1

Cites

245 of 245 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Retracted
Mechanisms 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
Microfluidic organs-on-chips
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
Fibrosis Progression in Nonalcoholic Fatty Liver vs Nonalcoholic Steatohepatitis: A Systematic Review and Meta-analysis of Paired-Biopsy Studies
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
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
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
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
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
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
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
Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: Implications for prognosis and clinical management
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
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
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
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
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
NAFLD and diabetes mellitus
Tilg, H., Moschen, A. R., & Roden, M. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.147 · Cited by 1,002
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 894
A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents
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
Three-Dimensional Cell Cultures in Drug Discovery and Development
Fang, Y., & Eglen, R. M. (2017) · SLAS Discovery · doi:10.1177/1087057117696795 · Cited by 849
Organoids-on-a-chip
Park, S. E., Georgescu, A., & Huh, D. (2019) · Science · doi:10.1126/science.aaw7894 · Cited by 847
Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies
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
Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors
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
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
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
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×
“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,…”
Background
Current and future pharmacological therapies for NAFLD/NASH
Sumida, Y., & Yoneda, M. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1415-1 · Cited by 686
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
Hepatocellular carcinoma in the absence of cirrhosis in United States Veterans is associated with nonalcoholic fatty liver disease
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
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 641
A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy
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
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
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
Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria
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
Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study
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
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
An Autophagy-Enhancing Drug Promotes Degradation of Mutant α 1 -Antitrypsin Z and Reduces Hepatic Fibrosis
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 603
Changes in the Prevalence of Hepatitis C Virus Infection, Nonalcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients With Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation
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
Ex Vivo 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
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
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
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
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
Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
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 511
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
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
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 449
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
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 424
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
Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation
Younossi, Z. M., Marchesini, G., Cortez‐Pinto, H., & Petta, S. (2018) · Transplantation · doi:10.1097/tp.0000000000002484 · Cited by 405
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
Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation
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
Disease modelling in human organoids
Lancaster, M. A., & Huch, M. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.039347 · Cited by 390
Bioprinted 3D Primary Liver Tissues Allow Assessment of Organ-Level Response to Clinical Drug Induced Toxicity In Vitro
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 389
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
Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
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 384
The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes
Gribkoff, V. K., & Kaczmarek, L. K. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.03.021 · Cited by 379
Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction
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
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
Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016
Moore, T. J., Zhang, H., Anderson, G., & Alexander, G. C. (2018) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2018.3931 · Cited by 356
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
α1-Antitrypsin deficiency
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 332
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
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
Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids
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
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
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 315
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 312
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 300
Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
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
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
Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing
Marx, U. (2016) · ALTEX · doi:10.14573/altex.1603161 · Cited by 295
Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle
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 279
Self-citation
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
Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model
Bauer, 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
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 268
3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade
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
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
Genetics of Phenylketonuria: Then and Now
Blau, N. (2016) · Human Mutation · doi:10.1002/humu.22980 · Cited by 244
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
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 239
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 233
Self-citation
Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis
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
Establishment 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 233
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 225
Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue
Esch, M. B., Ueno, H., Applegate, D. R., & Shuler, M. L. (2016) · Lab on a Chip · doi:10.1039/c6lc00461j · Cited by 224
Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies
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
In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system
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
Liver ‘organ on a chip’
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 216
Self-citation
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
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 211
Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit
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 204
Hepatic 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
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
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
An FDA/CDER perspective on nonclinical testing strategies: Classical toxicology approaches and new approach methodologies (NAMs)
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
Enhancing the functional maturity of induced pluripotent stem cell–derived human hepatocytes by controlled presentation of cell–cell interactions in vitro
Berger, D. R., Ware, B. R., Davidson, M. D., Allsup, S. R., & Khetani, S. R. (2014) · Hepatology · doi:10.1002/hep.27621 · Cited by 196
Gene Expression Predicts Histological Severity and Reveals Distinct Molecular Profiles of Nonalcoholic Fatty Liver Disease
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 195
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
Correction: Corrigendum: Functional Coupling of Human Microphysiology Systems: Intestine, Liver, Kidney Proximal Tubule, Blood-Brain Barrier and Skeletal Muscle
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
Self-citation
Disease 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 185
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 181
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 173
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 172
Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids
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 168
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 164
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
Evaluation of a microfluidic based cell culture platform with primary human hepatocytes for the prediction of hepatic clearance in human
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
Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6
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
Self-citation
Development 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
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 152
Liver microphysiological systems development guidelines for safety risk assessment in the pharmaceutical industry
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
Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery
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 147
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 147
Editor’s Highlight: Modeling Compound-Induced FibrogenesisIn VitroUsing Three-Dimensional Bioprinted Human Liver Tissues
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 146
Tissue 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 143
Establishment of a highly differentiated immortalized human cholangiocyte cell line with SV40T and hTERT
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
Control of oxygen tension recapitulates zone-specific functions in human liver microphysiology systems
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
Self-citation
A glass-based, continuously zonated and vascularized human liver acinus microphysiological system (vLAMPS) designed for experimental modeling of diseases and ADME/TOX
Li, X., George, S. M., Vernetti, L. A., Gough, A., & Taylor, D. L. (2018) · Lab on a Chip · doi:10.1039/c8lc00418h · Cited by 141
Self-citation
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 141
Drug‐induced cholestasis
Sundaram, V., & Björnsson, E. S. (2017) · Hepatology Communications · doi:10.1002/hep4.1088 · Cited by 138
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 136
Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure
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 131
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
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
Quantitative Assessment of Population Variability in Hepatic Drug Metabolism Using a Perfused Three-Dimensional Human Liver Microphysiological System
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
Directed differentiation of human induced pluripotent stem cells into functional cholangiocyte-like cells
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 119
Integrated in vitro models for hepatic safety and metabolism: evaluation of a human Liver-Chip and liver spheroid
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
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
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 111
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
Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism
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 106
Characterization of cultured cholangiocytes isolated from livers of patients with primary sclerosing cholangitis
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
A Toxicology for the 21st Century—Mapping the Road Ahead
Härtung, T. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp059 · Cited by 105
Factors associated with failure of oncology drugs in late-stage clinical development: A systematic review
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 104
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 103
Self-citation
Gene Regulatory Network Analysis and Engineering Directs Development and Vascularization of Multilineage Human Liver Organoids
Velazquez, J. J., LeGraw, R., Moghadam, F., Tan, Y., Kilbourne, J. A., Maggiore, J. C., Hislop, J., Liu, S., Cats, D., Lopes, S. M. C. D. S., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.11.002 · Cited by 103
Self-citation
Pro-fibrotic compounds induce stellate cell activation, ECM-remodelling and Nrf2 activation in a human 3D-multicellular model of liver fibrosis
Prestigiacomo, V., Weston, A. A., Messner, S., Lampart, F. L., & Suter‐Dick, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179995 · Cited by 102
Statins 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
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 100
On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships
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 100
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
Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines
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 95
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
Modeling Therapeutic Antibody–Small Molecule Drug-Drug Interactions Using a Three-Dimensional Perfusable Human Liver Coculture Platform
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
Pre-clinical and clinical investigations of metabolic zonation in liver diseases: The potential of microphysiology systems
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 94
Self-citation
Induced pluripotent stem cells model personalized variations in liver disease resulting from α1‐antitrypsin deficiency
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
Navigating 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 90
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
Comprehensive Evaluation of Organotypic and Microphysiological Liver Models for Prediction of Drug-Induced Liver Injury
Zhou, Y., Shen, J. X., & Lauschke, V. M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01093 · Cited by 85
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
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
Human adult hepatocytes in primary monolayer culture
Grant, M. H., Burke, M. D., HAWKSWORTH, G. M., Duthie, S. J., ENGESET, J., & Petrie, J. C. (1987) · Biochemical Pharmacology · doi:10.1016/0006-2952(87)90596-x · Cited by 84
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
Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology
Watson, D. E., Hunziker, R., & Wikswo, J. P. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217732765 · Cited by 84
Towards a three-dimensional microfluidic liver platform for predicting drug efficacy and toxicity in humans
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
Self-citation
HeLiVa platform: integrated heart-liver-vascular systems for drug testing in human health and disease
Vunjak‐Novakovic, G., Bhatia, S. N., Chen, C. S., & Hirschi, K. K. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt369 · Cited by 83
Bioprinted liver provides early insight into the role of Kupffer cells in TGF-β1 and methotrexate-induced fibrogenesis
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 81
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 81
Alpha-1-antitrypsin deficiency: Genetic variations, clinical manifestations and therapeutic interventions
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 80
Why Drugs Fail in Late Stages of Development: Case Study Analyses from the Last Decade and Recommendations
Parasrampuria, D. A., Benet, L. Z., & Sharma, A. (2018) · The AAPS Journal · doi:10.1208/s12248-018-0204-y · Cited by 80
1-Antitrypsin deficiency
Stoller, J. K. (2004) · Thorax · doi:10.1136/thorax.2003.017517 · Cited by 79
A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions
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
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
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
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 76
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
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 73
High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions
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
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 69
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 69
Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development
Davidson, M. D., Kukla, D. A., & Khetani, S. R. (2017) · Integrative Biology · doi:10.1039/c7ib00027h · Cited by 67
Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients
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
Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone
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
Prevention of cardiovascular disease through reduction of glycaemic exposure in type 2 diabetes: A perspective on glucose‐lowering interventions
Roussel, R., Steg, P. G., Mohammedi, K., Marre, M., & Potier, L. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13033 · Cited by 66
A 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 64
Self-citation
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 64
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 64
Self-citation
Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity
Choudhury, 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
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
The NIH microphysiological systems program: developing in vitro tools for safety and efficacy in drug development
Tagle, D. A. (2019) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2019.09.007 · Cited by 61
Liver Zonation
Colnot, S., & Perret, C. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-7107-4_2 · Cited by 58
A Model of Dormant-Emergent Metastatic Breast Cancer Progression Enabling Exploration of Biomarker Signatures
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
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 55
Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis
Li, J., Zhao, Y.-R., & Tian, Z. (2019) · World Journal of Hepatology · doi:10.4254/wjh.v11.i5.412 · Cited by 55
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
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 51
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
Physiological potential of cytokines and liver damages
Mannaa, F. A. E., & Abdel-Wahhab, K. G. (2016) · Hepatoma Research · doi:10.20517/2394-5079.2015.58 · Cited by 50
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
Self-citation
Organotypic and Microphysiological Models of Liver, Gut, and Kidney for Studies of Drug Metabolism, Pharmacokinetics, and Toxicity
Shen, 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 49
Analysis of an Integrated Human Multiorgan Microphysiological System for Combined Tolcapone Metabolism and Brain Metabolomics
Wang, X., Cirit, M., Wishnok, J. S., Griffith, L. G., & Tannenbaum, S. R. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b02224 · Cited by 48
Advanced Organ-on-a-Chip Devices to Investigate Liver Multi-Organ Communication: Focus on Gut, Microbiota and Brain
Boeri, L., Izzo, L., Sardelli, L., Tunesi, M., Albani, D., & Giordano, C. (2019) · Bioengineering · doi:10.3390/bioengineering6040091 · Cited by 47
A Perspective on Implementing a Quantitative Systems Pharmacology Platform for Drug Discovery and the Advancement of Personalized Medicine
Stern, A. M., Schurdak, M. E., Bahar, İ., Berg, J. M., & Taylor, D. L. (2016) · SLAS DISCOVERY · doi:10.1177/1087057116635818 · Cited by 47
Self-citation

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).

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
Bioprinting of Complex Multicellular Organs with Advanced Functionality—Recent Progress and Challenges Ahead
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

See all 122

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
ORCID: Gough, Albert
Vernetti, Lawrence
Ebrahimkhani, Mo R.
Stern, Andrew M.
Taylor, D. Lansing
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2020-12-17
Volume: 18
Issue: 4
Pages: 252-268
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/s41575-020-00386-1
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

Human biomimetic liver microphysiology systems in drug development and precision medicine

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks