Towards improved hepatocyte cultures: Progress and limitations
Abstract
Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market. Therefore, there is an urgent need for reliable predictive in vitro tests, which unfailingly identify hepatotoxic drug candidates, reduce drug development time, expenses and the number of test animals. Currently, human hepatocytes represent the gold standard. However, the use of hepatocytes is challenging since the cells are not constantly available and lose their metabolic activity in culture. To solve these problems many different approaches have been developed in the past decades. The aim of this review is to present these approaches and to discuss the possibilities and limitations as well as future opportunities and directions.
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Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market.
“Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market.1)”
From Cryopreservation of Hepatocyte Organoid-Derived Cells Generated from Human iPS Cells (2025) · cites this paper as [1]
The predictive accuracy of hepatotoxicity in animal studies is only 50%.
“However, the predictive accuracy of hepatotoxicity in animal studies is only 50%.1,5)”
From Cryopreservation of Hepatocyte Organoid-Derived Cells Generated from Human iPS Cells (2025) · cites this paper as [1]
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Cryopreservation of Hepatocyte Organoid-Derived Cells Generated from Human iPS Cells
Nagai, W., Inui, J., Ueyama-Toba, Y., Asano, R., & Mizuguchi, H. (2025) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b25-00276 · Cited by 1 · see citing works
- Authors
- Ruoß, M., Vosough, M., Königsrainer, A., Nadalin, S., Wagner, S., Sajadian, S., Huber, D., Heydari, Z., Ehnert, S., Hengstler, J. G., & Nussler, A. K.
- Affiliations
- University of Tübingen (DE)
- Royan Institute (IR)
- Universitätsklinikum Tübingen (DE)
- TU Dortmund University (DE)
- Corresponding author
- Nussler, Andreas K.
- ORCID
- Venue
- Food and Chemical Toxicology
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 138
- Pages
- 111188
- ISSN
- 0278-6915 (ISSN-L)
- OpenAlex
- W3004473610
- Cited by
- 77
- References
- 18
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 8 · 2023: 15 · 2022: 15 · 2021: 16 · 2020: 7
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Federal Ministry for Economic Affairs and Energy (ZF 4301401CS6)
- Ministry for Rural Areas and Consumer Protection Baden-Württemberg (BW 05110214)
- 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
- hepatocyte culture, human hepatocytes, hepatotoxicity, drug safety testing, in vitro toxicity prediction, alternatives to animal testing
- MeSH terms
- Drug Development, Cell Line, Cell Survival, Culture Media, Humans, Liver Failure, Acute, Spheroids, Cellular, Coculture Techniques, Cell Culture Techniques, Hepatocytes, Models, Animal, Cell Proliferation, Tissue Scaffolds, Chemical and Drug Induced Liver Injury, Activation, Metabolic
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