ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Contextualizing Hepatocyte Functionality of Cryopreserved HepaRG Cell Cultures.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
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- Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism.Toxicology letters · 2025Article
- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- 3D Hepatocyte Model with Composite Nanofibers That Reproduced Human In Vivo Drug Clearance Profiles.ACS pharmacology & translational science · 2025Article
- Development of a CYP2D6-enhanced HepaRG cell model with improved CYP2D6 metabolic capacity.PloS one · 2025Article
- Changes in cultivation parameters impact cytochrome P450 gene transcription in HepaRG cells: implications forFrontiers in pharmacology · 2025Article
- The Development of a 3D PET Fibrous Scaffold Modified with an Umbilical Cord dECM for Liver Tissue Engineering.Polymers · 2024Article
- Development of a human liver microphysiological coculture system for higher throughput chemical safety assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Identification of human pregnane X receptor antagonists utilizing a high-throughput screening platform.Frontiers in pharmacology · 2024Article
- A Comprehensive Evaluation of the Effects of RNA-Editing Proteins ADAR and ADARB1 on the Expression of the Drug-Metabolizing Enzymes in HepaRG Cells.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations.Bioengineering (Basel, Switzerland) · 2023Article
- Extended lifespan and improved genome stability in HepaRG-derived cell lines through reprogramming by high-density stress.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Liver three-dimensional cellular models for high-throughput chemical testing.Cell reports methods · 2023Review
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Article
- Oxidative-stress and long-term hepatotoxicity: comparative study in Upcyte human hepatocytes and hepaRG cells.Archives of toxicology · 2022Article
- Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains forFrontiers in toxicology · 2022Review
- Phenobarbital Induces SLC13A5 Expression through Activation of PXR but Not CAR in Human Primary Hepatocytes.Cells · 2021Article
- Three-Dimensional Liver Culture Systems to Maintain Primary Hepatic Properties for Toxicological Analysis In Vitro.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format of HepaRG cells (termed here "cryo-HepaRG") has emerged as a new model that improves global availability and experimental flexibility; however, it is largely unknown whether HepaRG cells in this format fully retain their hepatic characteristics. Therefore, we systematically investigated the hepatocyte functionality of cryo-HepaRG cultures in context with the range of interindividual variation observed with PHH in both sandwich-culture and suspension formats. These evaluations uncovered a novel adaptation period for the cryo-HepaRG format and demonstrated the impact of extracellular matrix on cryo-HepaRG functionality. Pharmacologically important drug-metabolizing alleles were genotyped in HepaRG cells and poor metabolizer alleles for CYP2D6, CYP2C9, and CYP3A5 were identified and consistent with higher frequency alleles found in individuals of Caucasian decent. We observed liver enzyme inducibility with aryl hydrocarbon receptor, constitutive androstane receptor (CAR), and pregnane X receptor activators comparable to that of sandwich-cultured PHH. Finally, we show for the first time that cryo-HepaRG supports proper CAR cytosolic sequestration and translocation to hepatocyte nuclei in response to phenobarbital treatment. Taken together, these data reveal important considerations for the use of this cell model and demonstrate that cryo-HepaRG are suitable for metabolism and toxicology screening.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.