Competency of different cell models to predict human hepatotoxic drugs
Abstract
Introduction The liver is the most important target for drug-induced toxicity. This vulnerability results from functional liver features and its role in the metabolic elimination of most drugs. Drug-induced liver injury is a significant leading cause of acute, chronic liver disease and an important safety issue when developing new drugs. Areas covered This review describes the advantages and limitations of hepatic cell-based models for early safety risk assessment during drug development. These models include hepatocytes cultured as monolayer, collagen-sandwich; emerging complex 3D configuration; liver-derived cell lines; stem cell-derived hepatocytes. Expert opinion In vitro toxicity assays performed in hepatocytes or hepatoma cell lines can potentially provide rapid and cost-effective early feedback to identify toxic candidates for compound prioritization. However, their capacity to predict hepatotoxicity depends critically on cells' functional performance. In an attempt to improve and prolong functional properties of cultured cells, different strategies to recreate the in vivo hepatocyte environment have been explored. 3D cultures, co-cultures of hepatocytes with other cell types and microfluidic devices seem highly promising for toxicological studies. Moreover, hepatocytes derived from human pluripotent stem cells are emerging cell-based systems that may provide a stable source of hepatocytes to reliably screen metabolism and toxicity of candidate compounds.
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PHHs are the best in vitro hepatocyte models in current drug discovery research.
“Primary (cryopreserved) human hepatocytes (PHHs) are the best in vitro hepatocyte models in current drug discovery research.7,8)”
From Cryopreservation of Hepatocyte Organoid-Derived Cells Generated from Human iPS Cells (2025) · cites this paper as [7]
Cites
Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells
Si-Tayeb, K., Noto, F. K., Nagaoka, M., Li, J., Battle, M. A., Duris, C., North, P. E., Dalton, S., & Duncan, S. A. (2010) · Hepatology · doi:10.1002/hep.23354 · Cited by 1,282 · see citing works
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Self-citationRecent advances in three‐dimensional multicellular spheroid culture for biomedical research
Lin, R., & Chang, H. (2008) · Biotechnology Journal · doi:10.1002/biot.200700228 · Cited by 1,264 · 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
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999 · see citing works
Björnsson, E. S., Bergmann, O. M., Björnsson, H. K., Kvaran, R. B., & Olafsson, S. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.02.006 · Cited by 865 · see citing works
Drug-Induced Acute Liver Failure: Results of a U.S. Multicenter, Prospective Study
Reuben, A., Koch, D. G., & Lee, W. M. (2010) · Hepatology · doi:10.1002/hep.23937 · Cited by 772 · see citing works
Hewitt, N. J., Gómez Lechón, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., Kenna, J. G., Gustavsson, L., Lohmann, C., Skonberg, C., et al. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530601093489 · Cited by 735 · see citing works
Self-citationAninat, C., Piton, A., Glaise, D., Charpentier, T. L., Langouët, S., Morel, F., Guguen‐Guillouzo, C., & Guillouzo, A. (2005) · Drug Metabolism and Disposition · doi:10.1124/dmd.105.006759 · Cited by 708 · see citing works
O’Brien, P. J., Irwin, W., Diaz, D., Howard-Cofield, E., Krejsa, C. M., Slaughter, M. R., Gao, B., Kaludercic, N., Angeline, A., Bernardi, P., et al. (2006) · Archives of Toxicology · doi:10.1007/s00204-006-0091-3 · Cited by 609 · see citing works
In vitro models for liver toxicity testing
Soldatow, V. Y., LeCluyse, E. L., Griffith, L. G., & Rusyn, I. (2012) · Toxicology Research · doi:10.1039/c2tx20051a · Cited by 482 · see citing works
Abboud, G., & Kaplowitz, N. (2007) · Drug Safety · doi:10.2165/00002018-200730040-00001 · Cited by 480 · see citing works
LeCluyse, E. L. (2001) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(01)00135-x · Cited by 477 · 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
Ramaiahgari, S., den Braver, M. W., Herpers, B., Terpstra, V., Commandeur, J. N. M., van de Water, B., & Price, L. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1215-9 · Cited by 363 · see citing works
Evaluation of HepaRG Cells as an in Vitro Model for Human Drug Metabolism Studies
Kanebratt, K. P., & Andersson, T. B. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.020016 · Cited by 355 · see citing works
Guo, L., Dial, S., Shi, L., Branham, W., Liu, J., Fang, J.-L., Green, B., Deng, H., Kaput, J., & Ning, B. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.035873 · Cited by 348 · see citing works
Li, A. P., Lu, C., Brent, J. A., Pham, C., Fackett, A., Ruegg, C. E., & Silber, P. M. (1999) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(99)00088-5 · Cited by 302 · see citing works
Design of artificial extracellular matrices for tissue engineering
Kim, B., Park, I., Hoshiba, T., Jiang, H., Choi, Y., Akaike, T., & Cho, C. (2010) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2010.10.001 · Cited by 297 · see citing works
Cell Lines: A Tool for In Vitro Drug Metabolism Studies
Gómez‐Lechón, M. J., Donato, M. T., Lahoz, A., & Castell, J. V. (2008) · Current Drug Metabolism · doi:10.2174/138920008783331086 · Cited by 297 · see citing works
Self-citationHepaRG Cells: A Human Model to Study Mechanisms of Acetaminophen Hepatotoxicity Δσ
McGill, M. R., Yan, H., Ramachandran, A., Murray, G. J., Rollins, D. E., & Jaeschke, H. (2010) · Hepatology · doi:10.1002/hep.24132 · Cited by 292 · see citing works
3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing
Takayama, K., Kawabata, K., Nagamoto, Y., Kishimoto, K., Tashiro, K., Sakurai, F., Tachibana, M., Kanda, K., Hayakawa, T., Furue, M. K., et al. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.11.029 · Cited by 289 · see citing works
McGinnity, D. F., Soars, M. G., Urbanowicz, R. A., & Riley, R. J. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.104.000026 · Cited by 272 · see citing works
Kostadinova, R., Boess, F., Applegate, D., Suter, L., Weiser, T., Singer, T., Naughton, B., & Roth, A. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.01.012 · Cited by 262 · see citing works
Human Hepatocytes in Primary Culture: The Choice to Investigate Drug Metabolism in Man
Gómez‐Lechón, M. J., Donato, M. T., Castell, J. V., & Jover, R. (2004) · Current Drug Metabolism · doi:10.2174/1389200043335414 · Cited by 253 · see citing works
Self-citationGeneration of Endoderm-Derived Human Induced Pluripotent Stem Cells From Primary Hepatocytes
Liu, H., Ye, Z., Kim, Y., Sharkis, S. J., & Jang, Y.-Y. (2010) · Hepatology · doi:10.1002/hep.23626 · Cited by 247 · see citing works
Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing
Tostões, R. M., Leite, S. B., Serra, M., Jensen, J., Björquist, P., Carrondo, M. J. T., Brito, C., & Alves, P. M. (2011) · Hepatology · doi:10.1002/hep.24760 · Cited by 246 · see citing works
Human hepatocytes as a tool for studying toxicity and drug metabolism
Gomez-Lechon, M., Donato, M., Castell, J., & Jover, R. (2003) · Current Drug Metabolism · doi:10.2174/1389200033489424 · Cited by 242 · see citing works
Self-citationGeneral Review on In Vitro Hepatocyte Models and Their Applications
Guguen‐Guillouzo, C., & Guillouzo, A. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-688-7_1 · Cited by 237 · see citing works
3D Organotypic Cultures of Human HepaRG Cells: A Tool for In Vitro Toxicity Studies
Gunness, P., Mueller, D., Shevchenko, V., Heinzle, E., Ingelman-Sundberg, M., & Noor, F. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft021 · Cited by 236 · 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
Maturation of Induced Pluripotent Stem Cell Derived Hepatocytes by 3D-Culture
Gieseck, R. L., Hannan, N. R. F., Bort, R., Hanley, N. A., Drake, R. A. L., Cameron, G. W. W., Wynn, T. A., & Vallier, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086372 · Cited by 198 · see citing works
New Technologies and Screening Strategies for Hepatotoxicity: Use of In Vitro Models
Dambach, D. M., Andrews, B. A., & Moulin, F. (2005) · Toxicologic Pathology · doi:10.1080/01926230590522284 · Cited by 176 · see citing works
Galactose-carrying polymers as extracellular matrices for liver tissue engineering
Cho, C. S., Seo, S. J., Park, I., Kim, S. H., Kim, T. H., Hoshiba, T., Harada, I., & Akaike, T. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.06.008 · Cited by 173 · see citing works
Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells.
Dai, Y., & Cederbaum, A. I. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09682-x · Cited by 169 · see citing works
Duan, Y., Ma, X., Zou, W., Wang, C. X., Behbahan, I. S., Ahuja, T. P., Tolstikov, V., & Zern, M. Α. (2010) · Stem Cells · doi:10.1002/stem.315 · Cited by 167 · 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
3D organotypic HepaRG cultures as in vitro model for acute and repeated dose toxicity studies
Mueller, D., Krämer, L., Hoffmann, E., Klein, S. G., & Noor, F. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.06.024 · Cited by 159 · see citing works
Liver tissue engineering in the evaluation of drug safety
Dash, A., Inman, W., Hoffmaster, K. A., Sevidal, S., Kelly, J., Obach, R. S., Griffith, L. G., & Tannenbaum, S. R. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250903160664 · Cited by 156 · see citing works
Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells
Anthérieu, S., Azzi, P. B.-E., Dumont, J., Abdel‐Razzak, Z., Guguen‐Guillouzo, C., Fromenty, B., Robin, M., & Guillouzo, A. (2012) · Hepatology · doi:10.1002/hep.26160 · Cited by 146 · see citing works
Opportunities for Use of Human iPS Cells in Predictive Toxicology
Anson, B. D., Kolaja, K. L., & Kamp, T. J. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.9 · Cited by 143 · see citing works
Developing High-Fidelity Hepatotoxicity Models From Pluripotent Stem Cells
Medine, C. N., Lucendo‐Villarin, B., Storck, C., Wang, F., Szkolnicka, D., Khan, F., Pernagallo, S., Black, J. R., Marriage, H. M., Ross, J. A., et al. (2013) · Stem Cells Translational Medicine · doi:10.5966/sctm.2012-0138 · Cited by 136 · see citing works
Etiologies and Outcomes of Acute Liver Failure in Germany
Hadem, J., Tacke, F., Bruns, T., Langgartner, J., Strnad, P., Denk, G., Fikatas, P., Manns, M. P., Hofmann, W. P., Gerken, G., et al. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.02.016 · Cited by 135 · see citing works
Li, C. Y., Stevens, K. R., Schwartz, R. E., Alejandro, B. S., Huang, J. H., & Bhatia, S. N. (2014) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0667 · Cited by 132 · see citing works
Goral, V. N., Hsieh, Y., Petzold, O. N., Clark, J. S., Yuen, P. K., & Faris, R. A. (2010) · Lab on a Chip · doi:10.1039/c0lc00135j · Cited by 131 · see citing works
Cytochromes P450 and Species Differences in Xenobiotic Metabolism and Activation of Carcinogen
Lewis, D. F., Ioannides, C., & Parke, D. V. (1998) · Environmental Health Perspectives · doi:10.1289/ehp.98106633 · Cited by 130 · see citing works
Three-dimensional culture of hepatocytes for prediction of drug-induced hepatotoxicity
Meng, Q. (2010) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425251003674356 · Cited by 130 · see citing works
Schyschka, L., Sánchez, J. M., Wang, Z., Burkhardt, B., Müller‐Vieira, U., Zeilinger, K., Bachmann, A., Nadalin, S., Damm, G., & Nussler, A. K. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1080-y · Cited by 128 · see citing works
Bruyn, T. D., Chatterjee, S., Fattah, S., Keemink, J., Nicolaï, J., Augustijns, P., & Annaert, P. (2013) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2013.773973 · Cited by 124 · see citing works
Lan, S.-F., Safiejko‐Mroczka, B., & Starly, B. (2010) · Toxicology in Vitro · doi:10.1016/j.tiv.2010.02.015 · Cited by 123 · see citing works
Tolosa, L., Pinto, S., Donato, M. T., Lahoz, A., Castell, J. V., O’Connor, J., & Gómez-Lechón, M. J. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs083 · Cited by 121 · see citing works
Self-citationSchoonen, W. G. E. J., Westerink, W. M. A., de Roos, J. A. D. M., & Débiton, E. (2005) · Toxicology in Vitro · doi:10.1016/j.tiv.2005.01.003 · Cited by 120 · see citing works
Yoshitomi, S., Ikemoto, K., Takahashi, J., Miki, H., Namba, M., & Asahi, S. (2001) · Toxicology in Vitro · doi:10.1016/s0887-2333(01)00011-x · Cited by 112 · see citing works
Proteomics Investigations of Drug-Induced Hepatotoxicity in HepG2 Cells
Summeren, A. V., Renes, J., Bouwman, F. G., Noben, J., van Delft, J. H. M., Kleinjans, J. C. S., & Mariman, E. C. M. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq380 · Cited by 108 · see citing works
Polarized expression of drug transporters in differentiated human hepatoma HepaRG cells
Vée, M. L., Noel, G. L., Jouan, E., Stieger, B., & Fardel, O. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.07.003 · Cited by 105 · see citing works
Hegde, M., Jindal, R., Bhushan, A., Bale, S. S., McCarty, W. J., Golberg, I., Usta, O. B., & Yarmush, M. L. (2014) · Lab on a Chip · doi:10.1039/c4lc00071d · Cited by 105 · see citing works
Three-Dimensional HepaRG Model As An Attractive Tool for Toxicity Testing
Leite, S. B., Wilk–Zasadna, I., Zaldivar, J. M., Airola, E., Reis-Fernandes, M. A., Mennecozzi, M., Guguen‐Guillouzo, C., Chesné, C., gualbert, G. C., Alves, P. M., et al. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs232 · Cited by 104 · see citing works
Drug-induced liver injury in 2007
Norris, W. E., Paredes, A. H., & Lewis, J. H. (2008) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3282f9764b · Cited by 104 · see citing works
Human and animal hepatocytes in vitro with extrapolation in vivo
O'Brien, P. J., Chan, K., & Silber, P. M. (2004) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2004.09.003 · Cited by 102 · see citing works
Miranda, J. P., Rodrigues, A., Tostões, R. M., Leite, S. B., Zimmerman, H., Carrondo, M. J. T., & Alves, P. M. (2010) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2009.0784 · Cited by 102 · see citing works
Effect of troglitazone on cytochrome P450 enzymes in primary cultures of human and rat hepatocytes
Sahi, J., Hamilton, G. A., Sinz, M., Barros, S., Huang, S. M., Lesko, L. J., & LeCluyse, E. L. (2000) · Xenobiotica · doi:10.1080/004982500237668 · Cited by 99 · see citing works
Stem cell-derived hepatocytes and their use in toxicology
Guguen‐Guillouzo, C., Corlu, A., & Guillouzo, A. (2009) · Toxicology · doi:10.1016/j.tox.2009.09.019 · Cited by 98 · see citing works
Donato, M. T., Jover, R., & Gómez‐Lechón, M. J. (2013) · Current Drug Metabolism · doi:10.2174/1389200211314090002 · Cited by 96 · see citing works
Self-citationMaintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells
Krause, P., Saghatolislam, F., Koenig, S., Unthan‐Fechner, K., & Probst, I. (2009) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-008-9166-1 · Cited by 93 · see citing works
Garside, H., Marcoe, K. F., Chesnut-Speelman, J., Foster, A. J., Muthas, D., Gerry Kenna, J., Warrior, U., Bowes, J., & Baumgartner, J. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.10.015 · Cited by 93 · see citing works
Hepatocyte-based in vitro model for assessment of drug-induced cholestasis
Chatterjee, S., Richert, L., Augustijns, P., & Annaert, P. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.10.032 · Cited by 91 · see citing works
Vignati, L., Turlizzi, E., Monaci, S., Grossi, P., de Kanter, R., & Monshouwer, M. (2005) · Toxicology · doi:10.1016/j.tox.2005.08.003 · Cited by 90 · see citing works
Tolosa, L., Gómez‐Lechón, M. J., Pérez-Cataldo, G., Castell, J. V., & Donato, M. T. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1012-x · Cited by 85 · see citing works
Self-citationInamori, M., Mizumoto, H., & Kajiwara, T. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0403 · 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
Species-specific toxicity of diclofenac and troglitazone in primary human and rat hepatocytes
Lauer, B., Tuschl, G., Kling, M., & Mueller, S. O. (2008) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2008.10.031 · Cited by 81 · see citing works
An update on metabolism studies using human hepatocytes in primary culture
Gómez-Lechón, M. J., Castell, J. V., & Donato, M. T. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.7.837 · Cited by 80 · see citing works
Self-citationCryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules
Terry, C., Hughes, R. D., Mitry, R. R., Lehec, S. C., & Dhawan, A. K. (2007) · Cell Transplantation · doi:10.3727/000000007783465000 · Cited by 79 · see citing works
Mature Human Hepatocytes from Ex Vivo Differentiation of Alginate-Encapsulated Hepatoblasts
Cheng, N., Wauthier, E., & Reid, L. M. (2008) · Tissue Engineering Part A · doi:10.1089/ten.a.2007.0131 · Cited by 78 · see citing works
Kobayashi, A., Yamakoshi, K., Yajima, Y., Utoh, R., Yamada, M., & Seki, M. (2013) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2013.05.034 · Cited by 78 · see citing works
Gustafsson, F., Foster, A. J., Sarda, S., Bridgland-Taylor, M. H., & Kenna, J. G. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kft223 · Cited by 77 · see citing works
Lepist, E., Gillies, H., Smith, W. R., Jia, H., Hubert, C., Claire, R. L. S., Brouwer, K. R., & Ray, A. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087548 · Cited by 77 · see citing works
No, D. Y., Lee, S.-A., Choi, Y. Y., Park, D., Jang, J. Y., Kim, D., & Lee, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050723 · Cited by 75 · see citing works
Alvetex®: Polystyrene Scaffold Technology for Routine Three Dimensional Cell Culture
Knight, E., Murray, B. A., Carnachan, R. J., & Przyborski, S. A. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-984-0_20 · Cited by 75 · see citing works
Stem cell‐derived hepatocytes as a predictive model for drug‐induced liver injury: are we there yet?
Kia, R., Sison-Young, R. L. C., Heslop, J. A., Kitteringham, N. R., Hanley, N. A., MILLS, J. S., Park, B. K., & Goldring, C. E. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04360.x · Cited by 74 · see citing works
Kotani, N., Maeda, K., Watanabe, T., Hiramatsu, M., Gong, L., Bi, Y., Takezawa, T., Kusuhara, H., & Sugiyama, Y. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.038968 · Cited by 74 · see citing works
Cell based approaches for evaluation of drug-induced liver injury
Greer, M. L., Barber, J., Eakins, J. A., & Kenna, J. G. (2009) · Toxicology · doi:10.1016/j.tox.2009.08.007 · Cited by 73 · see citing works
Classification of Hepatotoxicants Using HepG2 Cells: A Proof of Principle Study
den Hof, W. F. P. M. V., Coonen, M. L. J., van Herwijnen, M. H. M., Brauers, K. J. J., Wodzig, W. K. W. H., van Delft, J. H. M., & Kleinjans, J. C. S. (2014) · Chemical Research in Toxicology · doi:10.1021/tx4004165 · Cited by 73 · see citing works
Burkard, A., Dähn, C., Heinz, S., Zutavern, A., Sonntag-Buck, V., Maltman, D. J., Przyborski, S. A., Hewitt, N. J., & Braspenning, J. (2012) · Xenobiotica · doi:10.3109/00498254.2012.675093 · Cited by 72 · see citing works
Kock, J. D., Ceelen, L. M., Spiegelaere, W. D., Casteleyn, C. R., Claes, P., Vanhaecke, T., & Rogiers, V. (2011) · Archives of Toxicology · doi:10.1007/s00204-011-0706-1 · Cited by 72 · see citing works
Assessing the Metabolic Competence of Sandwich-Cultured Mouse Primary Hepatocytes
Mathijs, K., Kienhuis, A. S., Brauers, K. J. J., Jennen, D. G. J., Lahoz, A., Kleinjans, J. C. S., & van Delft, J. H. M. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.025775 · Cited by 72 · see citing works
Evaluation of Human Hepatocytes Cultured by Three-dimensional Spheroid Systems for Drug Metabolism
Ohkura, T., Ohta, K., Nagao, T., Kusumoto, K., Koeda, A., Ueda, T., Jomura, T., Ikeya, T., Ozeki, E., Wada, K., et al. (2014) · Drug Metabolism and Pharmacokinetics · doi:10.2133/dmpk.dmpk-13-rg-105 · Cited by 71 · see citing works
Yi, F., Liu, G., & Belmonte, J. C. I. (2012) · Protein & Cell · doi:10.1007/s13238-012-2918-4 · Cited by 71 · see citing works
Three-Dimensional Perfusion Bioreactor Culture Supports Differentiation of Human Fetal Liver Cells
Schmelzer, E., Triolo, F., Turner, M. E., Thompson, R. L., Zeilinger, K., Reid, L. M., Gridelli, B. G., & Gerlach, J. C. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0569 · Cited by 70 · see citing works
Generating hepatic cell lineages from pluripotent stem cells for drug toxicity screening
Baxter, M. A., Rowe, C., Alder, J. E., Harrison, S. P., Hanley, K. P., Park, B. K., Kitteringham, N. R., Goldring, C. E., & Hanley, N. A. (2010) · Stem Cell Research · doi:10.1016/j.scr.2010.02.002 · Cited by 66 · see citing works
Hepatospheres: Three dimensional cell cultures resemble physiological conditions of the liver
van Zijl, F., & Mikulits, W. (2010) · World Journal of Hepatology · doi:10.4254/wjh.v2.i1.1 · Cited by 65 · see citing works
Guzzardi, M. A., Vozzi, F., & Ahluwalia, A. D. (2009) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0695 · Cited by 62 · see citing works
Functional Assessment of the Quality of Human Hepatocyte Preparations for Cell Transplantation
Donato, M. T., Lahoz, A., Montero, S., Ana Bonora-Centelles, A., Pareja, E., Mir, J., Castell, J. V., & Gómez-Lechón, M. J. (2008) · Cell Transplantation · doi:10.3727/096368908787236620 · Cited by 62 · see citing works
Self-citationPrimary hepatocytes as a model to analyze species-specific toxicity and drug metabolism
Tuschl, G., Lauer, B., & Mueller, S. O. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.7.855 · Cited by 62 · see citing works
Metabolic Characterization of Primary Rat Hepatocytes Cultivated in Parallel Microfluidic Biochips
Legendre, A., Baudoin, R., Alberto, G., Paullier, P., Naudot, M., Bricks, T., Brocheton, J., Jacques, S., Cotton, J., & Leclerc, É. (2013) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23466 · Cited by 60 · see citing works
Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes
Marion, T. L., Perry, C. H., Claire, R. L. S., & Brouwer, K. L. R. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.02.002 · Cited by 59 · see citing works
Jetten, M. J. A., Kleinjans, J. C. S., Claessen, S. M. H., Chesné, C., & van Delft, J. H. M. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.07.010 · Cited by 57 · see citing works
Laurent, V., Fraix, A., Montier, T., Cammas‐Marion, S., Ribault, C., Benvegnu, T. J., Jaffrès, P., & Loyer, P. (2010) · Biotechnology Journal · doi:10.1002/biot.200900255 · Cited by 56 · see citing works
Leite, S. B., Teixeira, A. P., Miranda, J. P., Tostões, R. M., Clemente, J. J., Sousa, M. F. Q., Carrondo, M. J. T., & Alves, P. M. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.02.002 · Cited by 53 · see citing works
Network Analysis of Primary Hepatocyte Dedifferentiation Using a Shotgun Proteomics Approach
Rowe, C., Goldring, C. E. P., Kitteringham, N. R., Jenkins, R. E., Lane, B. S., Sanderson, C., Elliott, V., Platt, V., Metcalfe, P., & Park, B. K. (2010) · Journal of Proteome Research · doi:10.1021/pr1001687 · Cited by 51 · see citing works
Nakamura, K., Kato, N., Aizawa, K., Mizutani, R., Yamauchi, J., & Tanoue, A. (2011) · The Journal of Toxicological Sciences · doi:10.2131/jts.36.625 · Cited by 48 · see citing works
Klein, S. G., Mueller, D., Schevchenko, V., & Noor, F. (2013) · Journal of Applied Toxicology · doi:10.1002/jat.2929 · Cited by 47 · see citing works
Uehara, T., Kiyosawa, N., Shimizu, T., Omura, K., Hirode, M., Imazawa, T., Mizukawa, Y., Ono, A., Miyagishima, T., Nagao, T., et al. (2008) · Human & Experimental Toxicology · doi:10.1177/0960327107087910 · Cited by 46 · see citing works
Sung, J. H., Choi, J., Kim, D., & Shuler, M. L. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22413 · Cited by 45 · see citing works
In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor
Mueller, D., Tascher, G., Müller‐Vieira, U., Knobeloch, D., Nussler, A. K., Zeilinger, K., Heinzle, E., & Noor, F. (2011) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.418 · Cited by 43 · see citing works
Kienhuis, A. S., Wortelboer, H. M., Maas, W., van Herwijnen, M. H. M., Kleinjans, J. C. S., van Delft, J. H. M., & Stierum, R. H. (2007) · Toxicology in Vitro · doi:10.1016/j.tiv.2007.01.010 · Cited by 42 · see citing works
Rodrigues, R. M., Bouhifd, M., Bories, G., Sacco, M. G., Gribaldo, L., Fabbri, M., Coecke, S., & Whelan, M. (2012) · Toxicology in Vitro · doi:10.1016/j.tiv.2012.12.004 · Cited by 41 · see citing works
Gómez-Lechón, M. J., Tolosa, L., Castell, J. V., & Donato, M. T. (2010) · Toxicology in Vitro · doi:10.1016/j.tiv.2010.07.018 · Cited by 39 · see citing works
Self-citationAlexandre, E., Baze, A., Parmentier, C., Desbans, C., Pekthong, D., Gerin, B., Wack, C., Bachellier, P., Heyd, B., Weber, J.-C., et al. (2012) · Xenobiotica · doi:10.3109/00498254.2012.676693 · Cited by 37 · see citing works
Tolosa, L., Donato, M. T., Pérez-Cataldo, G., Castell, J. V., & Gómez-Lechón, M. J. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.11.008 · Cited by 36 · see citing works
Self-citationHashizume, T., Yoshitomi, S., Asahi, S., Uematsu, R., Matsumura, S., Chatani, F., & Oda, H. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq154 · Cited by 33 · see citing works
Guo, C., He, L., Yao, D., Aa, J., Cao, B., Ren, J., Wang, G., & Pan, G. (2013) · Toxicology Letters · doi:10.1016/j.toxlet.2013.09.019 · Cited by 32 · see citing works
Ohno, M., Motojima, K., Okano, T., & Taniguchi, A. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2007.0160 · Cited by 31 · see citing works
Lau, T. T., Lee, L. Q. P., Leong, W., & Wang, D. (2012) · Biomedical Materials · doi:10.1088/1748-6041/7/6/065003 · Cited by 31 · see citing works
Aritomi, K., Ishitsuka, Y., Tomishima, Y., Shimizu, D., Abe, N., Shuto, T., Irikura, M., Kai, H., & Irie, T. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13135fp · Cited by 30 · see citing works
Adverse Outcome Pathway-based Screening Strategies for an Animal-free Safety Assessment of Chemicals
Landesmann, B., Mennecozzi, M., Berggren, E., & Whelan, M. (2013) · Alternatives to Laboratory Animals · doi:10.1177/026119291304100609 · Cited by 30 · see citing works
Schoonen, W. G. E. J., Stevenson, J. C. R., Westerink, W. M. A., & Horbach, G. J. (2012) · Toxicology in Vitro · doi:10.1016/j.tiv.2012.01.004 · Cited by 27 · see citing works
Pal, R., Mamidi, M. K., Das, A. K., Gupta, P. K., & Bhonde, R. R. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23391 · Cited by 26 · see citing works
Induced pluripotent stem cell-derived hepatocytes as an alternative to human adult hepatocytes.
Hernandez, I., Baio, J. M., Tsay, E., Martinez, A. F., Fuentes, T. I., Bailey, L. L., Hasaniya, N. W. M. A., & Kearns‐Jonker, M. (2012) · PubMed Central · Cited by 22 · see citing works
Hepatic differentiation of pluripotent stem cells
Loya, K., Eggenschwiler, R., Ko, K., Sgodda, M., André, F., Bleidißel, M., Schöler, H. R., & Cantz, T. (2009) · Biological Chemistry · doi:10.1515/bc.2009.120 · Cited by 20 · see citing works
Tolosa, L., Ana Bonora-Centelles, A., Donato, M. T., Mirabet, V., Pareja, E., Negro, A., López, S. A., Castell, J. V., & Gómez-Lechón, M. J. (2011) · Transplantation · doi:10.1097/tp.0b013e31821aba37 · Cited by 19 · see citing works
Self-citationTamoxifen cytotoxicity in hepatoblastoma cells stably transfected with human CYP3A4
Hołownia, A., & Braszko, J. J. (2003) · Biochemical Pharmacology · doi:10.1016/j.bcp.2003.10.027 · Cited by 17 · see citing works
Hwan-Mook, K. I. M., Han, S., Hyun, B., Chang-Joon, A. H. N., Young-Nam, C. H. A., Jeong, K., & Oh, G.-T. (1995) · The Journal of Toxicological Sciences · doi:10.2131/jts.20.5_565 · Cited by 14 · see citing works
3D Hepatic In Vitro Models as Tools for Toxicity Studies
Mueller, D., Heinzle, E., & Noor, F. (2013) · Current Tissue Engineering · doi:10.2174/2211542011302010007 · Cited by 12 · see citing works
Kang, S. J., Jeong, S., Kim, E.-J., Cho, J.-H., Park, Y., Park, S., Shin, H.-S., Son, S., & Kang, H. (2012) · Cell Biology and Toxicology · doi:10.1007/s10565-012-9223-0 · Cited by 12 · see citing works
Genomic Consequences of Cytochrome P450 2C9 Overexpression in Human Hepatoma Cells
Narjoz, C., Marisa, L., Imbeaud, S., Paris, A., Delacroix, H., Beaune, P. H., & de Waziers, I. (2009) · Chemical Research in Toxicology · doi:10.1021/tx800417u · Cited by 11 · see citing works
Tania, M., Hsu, M. N., Png, S. N., Leo, H. L., Toh, G. W., & Birgersson, E. (2014) · Biotechnology Progress · doi:10.1002/btpr.1867 · Cited by 7 · see citing works
Uptake of Taurocholic Acid in Human Hepatocytes Isolated From Livers of Donors of Different Age
Olinga, P., Merema, M. T., Sandker, G. W., Slooff, M. J. H., Meijer, D. K. F., & Groothuis, G. M. M. (1998) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-199809000-00021 · Cited by 5 · see citing works
Bone marrow cell death and proliferation: Controlling mechanisms in normal and leukemic state
Kurata, M. (2013) · World Journal of Hematology · doi:10.5315/wjh.v2.i1.1 · Cited by 3 · see citing works
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Bell, C. C., Hendriks, D. F. G., Moro, S. M. L., Ellis, E., Walsh, J., Renblom, A., Fredriksson Puigvert, L., Dankers, A. C. A., Jacobs, F., Snoeys, J., et al. (2016) · Scientific Reports · doi:10.1038/srep25187 · Cited by 739 · see citing works
Bell, C. C., Dankers, A. C. A., Lauschke, V. M., Sison-Young, R., Jenkins, R., Rowe, C., Goldring, C. E., Park, K., Regan, S. L., Walker, T., et al. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfx289 · Cited by 327 · see citing works
Lauschke, V. M., Hendriks, D. F. G., Bell, C. C., Andersson, T. B., & Ingelman-Sundberg, M. (2016) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.6b00150 · Cited by 226 · see citing works
Long-term functional maintenance of primary human hepatocytes in vitro
Xiang, C., Du, Y., Meng, G., Soon Yi, L., Sun, S., Song, N., Zhang, X., Xiao, Y., Wang, J., Yi, Z., et al. (2019) · Science · doi:10.1126/science.aau7307 · Cited by 223 · see citing works
Toxicology Strategies for Drug Discovery: Present and Future
Blomme, E. A. G., & Will, Y. (2015) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.5b00407 · Cited by 196 · see citing works
Bell, C. C., Lauschke, V. M., Vorrink, S. U., Palmgren, H., Duffin, R., Andersson, T. B., & Ingelman-Sundberg, M. (2017) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.074369 · Cited by 189 · see citing works
Vorrink, S. U., Zhou, Y., Ingelman-Sundberg, M., & Lauschke, V. M. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy058 · Cited by 187 · see citing works
Vorrink, S. U., Ullah, S., Schmidt, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman‐Sundberg, M., & Lauschke, V. M. (2017) · The FASEB Journal · doi:10.1096/fj.201601375r · Cited by 172 · see citing works
Naturally-Derived Biomaterials for Tissue Engineering Applications
Brovold, M., Almeida, J. I., Plá-Palacín, I., Sainz‐Arnal, P., Sánchez‐Romero, N., Rivas, J. J., Almeida, H., Dachary, P. R., Serrano, T., Söker, S., et al. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0947-2_23 · Cited by 163 · see citing works
Characterization of a functional C3A liver spheroid model
Gaskell, H., Sharma, P., Colley, H. E., Murdoch, C., Williams, D. P., & Webb, S. D. (2016) · Toxicology Research · doi:10.1039/c6tx00101g · 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 131 · see citing works
Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines
Boon, R., Kumar, M., Tricot, T., Elia, I., Ordovás, L., Jacobs, F., One, J., Smedt, J. D., Eelen, G., Bird, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15058-6 · Cited by 118 · see citing works
Human Organoids for Predictive Toxicology Research and Drug Development
Matsui, T., & Shinozawa, T. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.767621 · Cited by 109 · see citing works
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 110 · see citing works
Organ-on-a-chip platforms for accelerating the evaluation of nanomedicine
Chen, X., Zhang, Y. S., Zhang, X., & Liu, C. (2020) · Bioactive Materials · doi:10.1016/j.bioactmat.2020.09.022 · Cited by 108 · see citing works
The potential of induced pluripotent stem cell derived hepatocytes
Hannoun, Z., Steichen, C., Dianat, N., Weber, A., & Dubart‐Kupperschmitt, A. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.025 · Cited by 103 · see citing works
Willemse, J., Verstegen, M. M. A., Vermeulen, A., Schurink, I. J., Roest, H. P., van der Laan, L. J. W., & de Jonge, J. (2020) · Materials Science and Engineering: C · doi:10.1016/j.msec.2019.110200 · Cited by 102 · see citing works
The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity
Lauschke, V. M., & Ingelman‐Sundberg, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101714 · Cited by 90 · see citing works
Assessing Toxicity with Human Cell-Based In Vitro Methods
Zink, D., Chuah, J. K. C., & Ying, J. Y. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.01.008 · Cited by 87 · see citing works
Gómez‐Lechón, M. J., Tolosa, L., & Donato, M. T. (2015) · Journal of Applied Toxicology · doi:10.1002/jat.3277 · Cited by 87 · see citing works
Self-citationZhou, Y., Shen, J. X., & Lauschke, V. M. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01093 · Cited by 85 · see citing works
Liver three-dimensional cellular models for high-throughput chemical testing
Yang, S., Ooka, M., Margolis, R. J., & Xia, M. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100432 · Cited by 75 · see citing works
Experimental liver models: From cell culture techniques to microfluidic organs‐on‐chip
Polidoro, M. A., Ferrari, E., Marzorati, S., Lleò, A., & Rasponi, M. (2021) · Liver International · doi:10.1111/liv.14942 · Cited by 76 · see citing works
Li, F., Cao, L., Parikh, S., & Zuo, R. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.02.021 · Cited by 72 · see citing works
Tolosa, L., Gómez-Lechón, M. J., López, S. A., Guzmán, C., Castell, J. V., Donato, M. T., & Jover, R. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw078 · Cited by 67 · see citing works
Self-citationPreclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction
Segovia‐Zafra, A., Zeo-Sánchez, D. E. D., Gomez, C. L., Pérez-Valdés, Z., García‐Fuentes, E., Andrade, R. J., Lucena, M. I., & Paz, M. V. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.013 · Cited by 71 · see citing works
Raschi, E. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i13.1761 · Cited by 68 · see citing works
Fong, E. L. S., Toh, T. B., Lin, Q. X. X., Liu, Z., Hooi, L., Rashid, M. B. M. A., Benoukraf, T., Chow, E. K., Huynh, T. H., & Yu, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.12.026 · Cited by 67 · see citing works
Kyffin, J. A., Sharma, P., Leedale, J., Colley, H. E., Murdoch, C., Mistry, P., & Webb, S. D. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.01.023 · Cited by 61 · see citing works
Kvist, A. J., Kanebratt, K. P., Walentinsson, A., Palmgren, H., O’Hara, M., Björkbom, A., Andersson, L. C., Ahlqvist, M. M., & Andersson, T. B. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.06.026 · Cited by 60 · see citing works
3D Cultivation Techniques for Primary Human Hepatocytes
Bachmann, A., Moll, M., Gottwald, E., Nies, C., Zantl, R., Wagner, H., Burkhardt, B., Sánchez, J., Ladurner, R., Thasler, W., et al. (2015) · Microarrays · doi:10.3390/microarrays4010064 · Cited by 59 · see citing works
Gómez-Lechón, M. J., & Tolosa, L. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1756-1 · Cited by 57 · see citing works
Self-citationCox, C. R., Lynch, S., Goldring, C. E., & Sharma, P. (2020) · Frontiers in Medical Technology · doi:10.3389/fmedt.2020.611913 · Cited by 57 · see citing works
Youhanna, S. C., Kemas, A. M., Preiss, L. C., Zhou, Y., Shen, J. X., Cakal, S. D., Paqualini, F. S., Goparaju, S. K., Shafagh, R. Z., Lind, J. U., et al. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000238 · Cited by 57 · see citing works
Liver-on-a-chip devices: the pros and cons of complexity
Dalsbecker, P., Adiels, C. B., & Goksör, M. (2022) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00346.2021 · Cited by 55 · see citing works
In Vitro Models for Studying Chronic Drug-Induced Liver Injury
Donato, M. T., Ferrer, G. G., & Tolosa, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911428 · Cited by 50 · see citing works
Self-citationAcetaminophen cytotoxicity is ameliorated in a human liver organotypic co-culture model
Nelson, L. J., Navarro, M., Treskes, P., Samuel, K., Tura-Ceide, O., Morley, S. D., Hayes, P. C., & Plevris, J. N. (2015) · Scientific Reports · doi:10.1038/srep17455 · Cited by 51 · see citing works
Shao, W., Xu, H., Zeng, K., Ye, M., Pei, R., & Wang, K. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04139-2 · Cited by 53 · see citing works
Bioprinting of Human Liver‐Derived Epithelial Organoids for Toxicity Studies
Bouwmeester, M., Bernal, P. N., Oosterhoff, L. A., van Wolferen, M. E., Lehmann, V., Vermaas, M., Buchholz, M., Peiffer, Q. C., Malda, J., van der Laan, L. J. W., et al. (2021) · Macromolecular Bioscience · doi:10.1002/mabi.202100327 · Cited by 49 · see citing works
Three-dimensional in vitro gut model on a villi-shaped collagen scaffold
Yi, B., Shim, K. Y., Ha, S. K., Han, J., Hoang, H.-H., Choi, I., Park, S., & Sung, J. H. (2017) · BioChip Journal · doi:10.1007/s13206-017-1307-8 · Cited by 46 · see citing works
Tolosa, L., Jiménez, N., Pérez, G., Castell, J. V., Gómez-Lechón, M. J., & Donato, M. T. (2017) · Archives of Toxicology · doi:10.1007/s00204-017-2036-4 · Cited by 44 · see citing works
Self-citationLucendo‐Villarin, B., Meseguer-Ripolles, J., Drew, J., Fischer, L., Ma, E., Flint, O. P., Simpson, K. J., Machesky, L. M., Mountford, J. C., & Hay, D. C. (2020) · Biofabrication · doi:10.1088/1758-5090/abbdb2 · Cited by 43 · see citing works
Characterisation of a functional rat hepatocyte spheroid model
Kyffin, J. A., Sharma, P., Leedale, J., Colley, H. E., Murdoch, C., Harding, A. L., Mistry, P., & Webb, S. D. (2018) · Toxicology in Vitro · doi:10.1016/j.tiv.2018.12.014 · Cited by 43 · see citing works
Wang, Z., Li, W., Jing, H., Ding, M., Fu, G., Yuan, T., Huang, W., Dai, M., Tang, D., Zeng, M., et al. (2019) · Theranostics · doi:10.7150/thno.34520 · Cited by 43 · see citing works
Microfluidic Liver-on-a-Chip for Preclinical Drug Discovery
Fu, J., Qiu, H., & Tan, C. S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041300 · Cited by 42 · see citing works
Cipriano, M., Correia, J. C., Camões, S. P., Oliveira, N., Cruz, P. E., Cruz, H. J., Castro, M., Ruas, J. L., Santos, J. M., & Miranda, J. P. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1901-x · Cited by 42 · see citing works
Weaver, R. J., Betts, C. J., Blomme, E. A. G., Gerets, H. H. J., Jensen, K. G., Hewitt, P. G., Juhila, S., Labbe, G., Liguori, M. J., Mesens, N., et al. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1341489 · Cited by 41 · see citing works
3D-bioprinted HepaRG cultures as a model for testing long term aflatoxin B1 toxicity in vitro
Schmidt, K., Berg, J., Röhrs, V., Kurreck, J., & Al‐Zeer, M. A. (2020) · Toxicology Reports · doi:10.1016/j.toxrep.2020.11.003 · Cited by 42 · see citing works
Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing
Jin, M., Xiao, Y., Liao, W., Chen, Q., Yang, W., Li, Y., Li, S., Gao, Y., Peng, Q., & Zhou, S. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02152-9 · Cited by 41 · see citing works
Hengstler, J. G., Sjogren, A.-K. M., Zink, D., & Hornberg, J. J. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02669-7 · Cited by 41 · see citing works
Multiparametric assay using HepaRG cells for predicting drug-induced liver injury
貴文, 富., Okamura, H., Satsukawa, M., Yokoi, T., & Konno, Y. (2015) · Toxicology Letters · doi:10.1016/j.toxlet.2015.04.014 · Cited by 38 · see citing works
High-Content Screening for the Detection of Drug-Induced Oxidative Stress in Liver Cells
Donato, M. T., & Tolosa, L. (2021) · Antioxidants · doi:10.3390/antiox10010106 · Cited by 40 · see citing works
Self-citationGe, Y., Yang, S., Zhang, T., Wan, X., Zhu, Y., Yang, F., Yin, L., Pu, Y., & Liang, G. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.165659 · Cited by 42 · see citing works
Stem-cell derived hepatocyte-like cells for the assessment of drug-induced liver injury
Donato, M. T., & Tolosa, L. (2019) · Differentiation · doi:10.1016/j.diff.2019.02.004 · Cited by 37 · see citing works
Self-citationBowen, T. J., Southam, A. D., Hall, A. R., Weber, R. J. M., Lloyd, G. R., Macdonald, R., Wilson, A., Pointon, A., & Viant, M. R. (2023) · Nature Communications · doi:10.1038/s41467-023-40333-7 · Cited by 36 · see citing works
Long-term and mechanistic evaluation of drug-induced liver injury in Upcyte human hepatocytes
Tolosa, L., Jiménez, N., Pelechá-Salvador, M., Castell, J. V., Gómez-Lechón, M. J., & Donato, M. T. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2349-y · Cited by 35 · see citing works
Self-citationSchaefer, M., Schänzle, G., Bischoff, D., & Süßmuth, R. D. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.067348 · Cited by 34 · see citing works
Basharat, A., Rollison, H. E., Williams, D. P., & Ivanov, D. P. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115279 · Cited by 36 · see citing works
Herzog, N., Hansen, M., Miethbauer, S., Schmidtke, K., Anderer, U., Lupp, A., Sperling, S., Seehofer, D., Damm, G., Scheibner, K., et al. (2015) · Cell Biology International · doi:10.1002/cbin.10574 · Cited by 33 · see citing works
Organs-on-chips and Its Applications
Sun, W., Chen, Y., Luo, G., Zhang, M., Zhang, H., Wang, Y., & Hu, P. (2016) · Chinese Journal of Analytical Chemistry · doi:10.1016/s1872-2040(16)60920-9 · Cited by 33 · see citing works
Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications
Xu, Q. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.730008 · Cited by 36 · see citing works
Chlorpyrifos induces cytotoxicity via oxidative stress and mitochondrial dysfunction in HepG2 cells
Montanarí, C., Franco-Campos, F., Taroncher, M., Rodríguez-Carrasco, Y., Zingales, V., & Ruiz, M.-J. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.114933 · Cited by 32 · see citing works
Hydrogel-Based Strategies for Liver Tissue Engineering
Zhang, Y., Li, L., Dong, L., Cheng, Y., Huang, X., Xue, B., Jiang, C., Cao, Y., & Yang, J. (2024) · Chem & Bio Engineering · doi:10.1021/cbe.4c00079 · Cited by 31 · see citing works
Development of Liver-on-Chip Integrating a Hydroscaffold Mimicking the Liver’s Extracellular Matrix
Messelmani, T., Goff, A. L., Souguir, Z., Maes, V., Roudaut, M., Vandenhaute, E., Maubon, N., Legallais, C., Leclerc, É., & Jellali, R. (2022) · Bioengineering · doi:10.3390/bioengineering9090443 · Cited by 29 · see citing works
Acetaminophen toxicity in rat and mouse hepatocytesin vitro
Kučera, O., Endlicher, R., Rychtrmoc, D., Lotková, H., Sobotka, O., & Červinková, Z. (2016) · Drug and Chemical Toxicology · doi:10.1080/01480545.2016.1255953 · Cited by 29 · see citing works
Guo, K., & van den Beucken, T. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01317-2 · Cited by 28 · see citing works
Li, L., Zang, Q., Li, X., Zhu, Y., Wen, S., He, J., Zhang, R., & Abliz, Z. (2023) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2023.04.007 · Cited by 28 · see citing works
Li, L., Chen, B., Yan, H., Zhao, Y., Lou, Z., Li, J., Fu, B., Zhu, X., McManus, D. P., Dai, J., et al. (2018) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0006309 · Cited by 27 · see citing works
Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
Handin, N., Mickols, E., Ölander, M., Rudfeldt, J., Blom, K., Nyberg, F., Senkowski, W., Urdzik, J., Maturi, V., Fryknäs, M., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103235 · Cited by 27 · see citing works
Use of human derived liver cells for the detection of genotoxins in comet assays
Mišík, M., Nersesyan, A. K., Ropek, N., Huber, W. W., Haslinger, E., & Knasmüller, S. (2018) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2018.12.003 · Cited by 27 · see citing works
Sphingolipid metabolism as a marker of hepatotoxicity in drug-induced liver injury
Li, L., Wang, H., & Jones, J. W. (2020) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2020.106484 · Cited by 25 · see citing works
Gómez-Lechón, M. J., Tolosa, L., & Donato, M. T. (2016) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1238459 · Cited by 26 · see citing works
Self-citationWang, Z., Li, W., Li, Q., Jing, H., Yuan, T., Fu, G., Tang, D., Zhang, H., Yan, H., & Zhai, B. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109010 · Cited by 23 · see citing works
BOTEON, Y. L., Wallace, L. M., Boteon, A. P. C. D. S., Mirza, D. F., Mergental, H., Bhogal, R. H., & Afford, S. C. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201419 · Cited by 23 · see citing works
Which concentrations are optimal for in vitro testing?
Albrecht, W. (2020) · EXCLI journal · doi:10.17179/excli2020-2761 · Cited by 22 · see citing works
Vitelli-Avelar, D. M., Sathler-Avelar, R., Mattoso-Barbosa, A. M., Gouin, N., Perdigão-de-Oliveira, M., Valério-dos-Reis, L., Costa, R. P., Elói-Santos, S. M., Gomes, M. D. S., do Amaral, L. R., et al. (2017) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0005233 · Cited by 22 · see citing works
Gosslau, A. (2016) · Food Science and Human Wellness · doi:10.1016/j.fshw.2016.05.003 · Cited by 23 · see citing works
In vitro cell-based models of drug-induced hepatotoxicity screening: progress and limitation
Mirahmad, M., Sabourian, R., Mahdavi, M. R., Larijani, B. A., & Safavi, M. (2022) · Drug Metabolism Reviews · doi:10.1080/03602532.2022.2064487 · Cited by 20 · see citing works
A pumpless liver-on-a-chip for drug hepatotoxicity analysis
Jiao, D., Xie, L., & Xing, W. (2024) · The Analyst · doi:10.1039/d4an00602j · Cited by 21 · see citing works
Recent advances in the development of in vitro liver models for hepatotoxicity testing
Lu, S., Zhang, J., Lin, S., Zheng, D., Shen, Y., Qin, J., Li, Y. Y., & Wang, S. (2021) · Bio-Design and Manufacturing · doi:10.1007/s42242-021-00142-7 · Cited by 21 · see citing works
Zingales, V., Fedeli, C., Fernández-Franzón, M., & Ruiz, M.-J. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111473 · Cited by 20 · see citing works
Donato, M. T., Gómez-Lechón, M. J., & Tolosa, L. (2016) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1271784 · Cited by 19 · see citing works
Self-citationPluripotent Stem Cell-Derived Human Tissue: Platforms to Evaluate Drug Metabolism and Safety
Meseguer-Ripolles, J., Khetani, S. R., Blanco, J. G., Iredale, M., & Hay, D. C. (2017) · The AAPS Journal · doi:10.1208/s12248-017-0171-8 · Cited by 18 · see citing works
3D Bioprinted Liver-on-a-Chip for Drug Cytotoxicity Screening
Huh, J., Parra, J. P. R. L. L., Copus, J. S., Kang, H., Bishop, C. E., Söker, S., Murphy, S. V., Shupe, T. D., Yoo, J. J., Lee, S. J., et al. (2023) · Tissue Engineering Part A · doi:10.1089/ten.tea.2023.0212 · Cited by 19 · see citing works
A shift in paradigm towards human biology‐based systems for cholestatic‐liver diseases
Noor, F. (2015) · The Journal of Physiology · doi:10.1113/jp271124 · Cited by 19 · see citing works
Expression of miRNA-122 Induced by Liver Toxicants in Zebrafish
Nam, H.-S., Hwang, K., Jeong, Y.-M., Ryu, J.-I., Choi, T. Y., Bae, M., Son, W., You, K., Son, H., & Kim, C. (2016) · BioMed Research International · doi:10.1155/2016/1473578 · Cited by 19 · see citing works
Tasnim, F., Singh, N. H., Tan, E. K. F., Xing, J., Li, H., Hissette, S., Manesh, S., Fulwood, J., Gupta, K., Ng, C. W., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61699-4 · Cited by 19 · see citing works
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Dame, K., & Ribeiro, A. J. S. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220959598 · Cited by 19 · see citing works
Sasikumar, S., Chameettachal, S., Kingshott, P., Cromer, B., & Pati, F. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.1c00994 · Cited by 18 · see citing works
Hussain, F., Basu, S., Heng, J. J. H., Loo, L., & Zink, D. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02778-3 · Cited by 18 · see citing works
Milner, E., Ainsworth, M., McDonough, M., Stevens, B. D., Buehrer, J., Delzell, R., Wilson, C., & Barnhill, J. C. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100060 · Cited by 19 · see citing works
Advancing hepatotoxicity assessment: current advances and future directions
Kim, Y., Kim, Y., & Kim, Y. (2025) · Toxicological Research · doi:10.1007/s43188-025-00289-w · Cited by 20 · see citing works
A new cell-sized support for 3D cell cultures based on recombinant spider silk fibers
Stern-Tal, D., Ittah, S., & Sklan, E. (2021) · Journal of Biomaterials Applications · doi:10.1177/08853282211037781 · Cited by 19 · see citing works
Ning, J., Chen, L., & Rietjens, I. M. C. M. (2019) · Food and Chemical Toxicology · doi:10.1016/j.fct.2019.110572 · Cited by 16 · see citing works
Liver regeneration biology: Implications for liver tumour therapies
Hadjittofi, C., Feretis, M., Martin, J. L., Harper, S., & Huguet, E. (2021) · World Journal of Clinical Oncology · doi:10.5306/wjco.v12.i12.1101 · Cited by 18 · see citing works
Niemeijer, M., Więcek, W., Fu, S., Huppelschoten, S., Bouwman, P., Baze, A., Parmentier, C., Richert, L., Paules, R. S., Bois, F. Y., et al. (2024) · Environmental Health Perspectives · doi:10.1289/ehp11891 · Cited by 16 · see citing works
Ma, X., Sun, J., Ye, Y., Ji, J., & Sun, X. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.150840 · Cited by 15 · see citing works
Sanchez-Quant, E., Richter, M. L., Colomé‐Tatché, M., & Martinez‐Jimenez, C. P. (2023) · Genome biology · doi:10.1186/s13059-023-03075-9 · Cited by 14 · see citing works
Nudischer, R., Renggli, K., Hierlemann, A. R., Roth, A. B., & Bertinetti‐Lapatki, C. (2020) · PLoS ONE · doi:10.1371/journal.pone.0235745 · Cited by 15 · see citing works
Jellali, R., Lereau, M., Tauran, Y., Gilard, F., Danoy, M., Kido, T., Miyajima, A., Sakai, Y., & Leclerc, É. (2019) · Differentiation · doi:10.1016/j.diff.2019.10.006 · Cited by 14 · see citing works
- Authors
- Gómez-Lechón, M. J., Tolosa, L., Conde, I., & Donato, M. T.
- Affiliations
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Instituto de Investigación Sanitaria La Fe (ES)
- Universitat de València (ES)
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa UK Limited
- Published
- 2014-10-09
- Volume
- 10
- Issue
- 11
- Pages
- 1553-1568
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- OpenAlex
- W2035459829
- Cited by
- 199
- References
- 129
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 19 · 2023: 17 · 2022: 16 · 2021: 23 · 2020: 25 · 2019: 16 · 2018: 16 · 2017: 14 · 2016: 18 · 2015: 12 · 2014: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatotoxicity, drug-induced liver injury, hepatocyte models, hepatocyte monolayer culture, hepatoma cell lines, stem cell-derived hepatocytes, pluripotent stem cells, co-culture, microfluidics, in vitro toxicity prediction, hepatocyte function
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Humans, Liver, Toxicity Tests, Hepatocytes, Cell Line, Tumor, Chemical and Drug Induced Liver Injury
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