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.