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HepaRG Cells as a Model for Hepatotoxicity Studies


The human HepaRG cell line has been established from a hepatocholangiocarcinoma and first described in 2002; it possesses bipotent properties allowing commitment into two cell lineages hepatocytes expressing various functions of mature hepatocytes and primitive biliary cells. HepaRG cells can retrodifferentiate and transdifferentiate. Mature HepaRG hepatocytes express most phase 1 (including the major cytochromes P450 3A4, 2B6, and 1A2) and phase 2 enzymes, as well as the main transporters involved in drug and bile acid metabolism and excretion, and exhibit appropriate responsiveness to prototypical inducers and inhibitors. They can remain functionally stable in a nonproliferative state for several weeks; meanwhile, they progress toward aging. HepaRG cells are widely used to investigate different types of chemical-induced hepatotoxicity, including cell death, cholestasis, steatosis, and phospholipidosis, as well as genotoxicity, after acute and/or repeated treatment with reference xenobiotics. Overall, they represent a reliable source of metabolically competent human liver cells, provide consistent responses to xenobiotics and, therefore, can be used as a surrogate to primary human hepatocytes for investigating drug metabolism parameters and both acute and chronic effects of xenobiotics in human liver. © 2018 John Wiley and Sons, Inc.
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hal-01875339 , version 1 (17-09-2018)



A. Guillouzo, C. Guguen-Guillouzo. HepaRG Cells as a Model for Hepatotoxicity Studies. Stem Cells in Birth Defects Research and Developmental Toxicology, Wiley Blackwell, pp.309-339, 2018, 9781119283249; 9781119283218. ⟨10.1002/9781119283249.ch12⟩. ⟨hal-01875339⟩
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