HepaRG: An Emerging In vitro Tool

Abstract

Safety of new drug candidates is routinely assessed by using in vitro hepatocyte models such as primary human hepatocytes (PHH) and establishedhuman liver cell lines. Although PHH remain the gold standard, their limited and unpredictable availability, inability to proliferate, rapid loss of drug metabolising enzymes and interindividual variability are major disadvantages. To overcome these problems, many human liver cell lines have been developed. These stable cell lines are easy to work with and are available in large quantities but they lack most of the liver-specific functions and present altered gene expression profiles. Despite these issues, some of these cell lines such as nontumorigenic immortalised cell line Fa2N4 and hepatoma cell line HepG2 are frequently used in preclinical testing. Recently, a new human liver cell line HepaRG, derived from a female hepatocarcinoma patient has been made available. Bipotent progenitor HepaRG cells differentiate into hepatocytes and biliary epithelial cells and exhibit capability of maintaining liver-specific functions. A genome-wide gene expression profile analysis showed greater similarities between PHH and HepaRG cells as compared to HepG2 cells [1]. Regulation of carbohydrate metabolism, production of albumin and lactate, elimination of sorbitol and galactose at comparable rates to PHH make HepaRG cells the best differentiated cell line available and an in vitro tool of choice [2].