ArticleBasic & clinical pharmacology & toxicology2017
Human Hepatic HepaRG Cells Maintain an Organotypic Phenotype with High Intrinsic CYP450 Activity/Metabolism and Significantly Outperform Standard HepG2/C3A Cells for Pharmaceutical and Therapeutic Applications.
Article in Basic & clinical pharmacology & toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Transcriptomic responses to repeated exposure of human C3A liver spheroids to polystyrene nanoplastics.Archives of toxicology · 2026Article
- SINEUP-mediated enhancement of HNF4α improves metabolic function in Huh7-based bioengineered hepatic microtissues.Journal of liver cancer · 2026Article
- Lentiviral-mediated expression of cytochrome P450 2D6 in HepaRG cells: new means for in vitro xenobiotic biotransformation and cellular response to chimeric viral mRNA.Archives of toxicology · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- The Role that Biobanks Can Play in Driving Animal-Free Biomedical Research.Expert reviews in molecular medicine · 2026Review
- Exploring the potential of liver microphysiological systems of varied configurations to model cholestatic chemical effects.Archives of toxicology · 2026Article
- Impact of ethanol as a vehicle for water-insoluble pollutants in BEAS-2B cell toxicity assays.Toxicology mechanisms and methods · 2025Article
- Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025Review
- Integrating Transcriptomic and Targeted New Approach Methodologies into a Tiered Framework for Chemical Bioactivity Screening.Environmental health perspectives · 2025Article
- Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Article
- MechanisticComputational and structural biotechnology journal · 2025Article
- Time-course characterization of whole-transcriptome dynamics of HepG2/C3A spheroids and its toxicological implications.Toxicology letters · 2024Article
- Advancing Toxicity Predictions: A Review onEnvironment & health (Washington, D.C.) · 2024Review
- Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Compound Absorption in Polymer Devices Impairs the Translatability of Preclinical Safety Assessments.Advanced healthcare materials · 2024Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Evaluation of drug-induced liver toxicity of trovafloxacin and levofloxacin in a human microphysiological liver model.Scientific reports · 2023Article
- Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro.Journal of clinical medicine · 2023Article
- Three-Dimensional Cell Co-Culture Liver Models and Their Applications in Pharmaceutical Research.International journal of molecular sciences · 2023Review
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conventional in vitro human hepatic models for drug testing are based on the use of standard cell lines derived from hepatomas or primary human hepatocytes (PHHs). Limited availability, interdonor functional variability and early phenotypic alterations in PHHs restrict their use, whilst standard cell lines such as HepG2 lack a substantial and variable set of liver-specific functions such as CYP450 activity. Alternatives include the HepG2-derivative C3A cells selected as a more differentiated and metabolically active hepatic phenotype. Human HepaRG cells are an alternative organotypic co-culture model of hepatocytes and cholangiocytes reported to maintain in vivo-like liver-specific functions, including intact Phase I-III drug metabolism. In this study, we compared C3A and human HepaRG cells using phenotypic profiling, CYP450 activity and drug metabolism parameters to assess their value as hepatic models for pre-clinical drug testing or therapeutics. Compared with C3As, HepaRG co-cultures exhibit a more organotypic phenotype, including evidence of hepatic polarity with the strong expression of CYP3A4, the major isoform involved in the metabolism of over 60% of marketed drugs. Significantly greater CYP450 activity and expression of CYP1A2, CYP2E1 and CYP3A4 genes in HepaRG cells (comparable with that of human liver tissue) was demonstrated. Moreover, HepaRG cells also preferentially expressed the hepatic integrin α
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