The DOI matches its Crossref record; 129 of the 129 references it cites were found in a registry or an index.
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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“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]
Citations
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
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
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
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
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
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
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
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
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
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
Research works printed but not linked: 4
- Ohkura T, 2014, Drug Metab Pharmacokinet
- Ramaiahgari SC, 2014, Arch Toxicol, 88, 1083
- Klein S, 2013, J Appl Toxicol
- Katsuda T, 2012, J Stem Cells, 7, 1
Cited by
Sorted by citations
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
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
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 241
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
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 201
Metadata
- 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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