Cited by 199Drug-Induced Hepatotoxicity and ProtectionAnimal testing and alternativesLiver physiology and pathology

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Competency of different cell models to predict human hepatotoxic drugs

Gómez-Lechón, M José, Tolosa, Laia, Conde, Isabel, Donato, M Teresa·2014·Expert Opinion on Drug Metabolism & Toxicology

DOI 10.1517/17425255.2014.967680

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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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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)
ORCID: Tolosa, Laia
Conde, Isabel
Donato, M Teresa
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
DOI: 10.1517/17425255.2014.967680
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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