ArticleArchives of toxicology2022
Optimisation of the HepaRG cell line model for drug toxicity studies using two different cultivation conditions: advantages and limitations.
Article in Archives of toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 19 citations in OpenAlex.
- Free Fatty acid-induced disruption of hepatic vitamin D metabolism impairs bone homeostasis in an in vitro 3D human liver-bone model.Archives of toxicology · 2026Article
- Cell line identity rather than medium composition determines transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media: comparison with primary human hepatocytes.Archives of toxicology · 2026Article
- A collagen hydrogel-based 3D Heparg model for enhanced hepatocyte function and assessment of cholestatic drug-induced liver injury.Archives of toxicology · 2026Article
- Red blood cell damage defines the etiology of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids.Acta pharmaceutica Sinica. B · 2026Article
- Article
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025Review
- Single-cell morphological tracking of cell states to identify small-molecule modulators of liver differentiation.iScience · 2025Article
- Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening.Archives of toxicology · 2025Article
- Alternatives to animal-derived extracellular matrix hydrogels? An explorative study with HepaRG cells in animal-free hydrogels under static and dynamic culture conditions.Frontiers in toxicology · 2025Article
- Changes in cultivation parameters impact cytochrome P450 gene transcription in HepaRG cells: implications forFrontiers in pharmacology · 2025Article
- Advancing Environmental ToxicologyEnvironment & health (Washington, D.C.) · 2024Review
- Effects of total saikosaponins on CYP3A4 and CYP1A2 in HepaRG cells.Experimental and therapeutic medicine · 2024Article
- Assessing the mitochondrial safety profile of the molnupiravir active metabolite, β-d-N4-hydroxycytidine (NHC), in the physiologically relevant HepaRG model.Toxicology research · 2024Article
- Genotoxicity assessment of eight nitrosamines using 2D and 3D HepaRG cell models.Archives of toxicology · 2023Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HepaRG cell line represents a successful model for hepatotoxicity studies. These cells are of human origin and are differentiated in vitro into mature and functional hepatocyte-like cells. The objective of this research was to compare two different culture protocols, Sison-Young et al. 2017 (hereinafter referred as Sison) and Gripon et al. 2002 (hereinafter referred as Biopredic) for HepaRG cells in order to optimise this model for drug metabolism and toxicity testing studies. HepaRG cells obtained from the same batch were cultured according to the described protocols. Using both protocols, differentiated HepaRG cells retained their drug metabolic capacity (major phase I/II enzymes) and transporters, as well as their morphological characteristics. Morphologically, HepaRG cells cultured after the Biopredic protocol formed more apical membranes and small ductular-like structures, than those cultivated using the Sison protocol. Also, the efflux activity of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) as well as the activity of uridine-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) were significantly reduced in HepaRG cultured using the Sison protocol. Applying well-established drug cocktails to measure cytochrome P450 (CYPs) activity, we found that production of the corresponding metabolites was hampered in Sison-cultured HepaRG cells, indicating that the activity of CYP1A2, CYP2C9, CYP3A4, CYP2B6 and CYP2C19 was significantly reduced. Moreover, HepaRG sensitivity to well-known drugs, namely diclofenac, amiodarone, imipramine and paracetamol, revealed some differences between the two culture protocols. Furthermore, the HepaRG cells can be maintained with higher viability and sufficient CYPs activity and expression (i.e. CYP3A4, CYP1A2 and CYP2B6) as well as liver-specific functions, using Biopredic compared with the Sison culture protocol. These maintained liver-specific functions might be dependent on the prolongation of the culture conditions in the case of the Biopredic protocol. In conclusion, based on the metabolic activity of HepaRG cells using the standard protocol from Biopredic, we believe that this protocol is optimal for investigating drug metabolism and pharmacokinetic screening studies.
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