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Hepatotoxicity: Measuring drug-induced mitochondrial toxicity in HepaRG™ cells using the Mito-ID® Extracellular O2 Sensor Kit

Valery Shevchenko, Biopredic International, Rennes, France

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Introduction

Cell type choice is a critical parameter in the design of an in vitro toxicological assessment. For hepatotoxicity, the benchmark is primary human hepatocytes; however, these cells are associated with the obvious limitations of access, lot-to-lot variability and cost. Cell lines such as HepG2, THLE and Fa2N-4 are therefore commonly used as a cheaper, more accessible alternative but these too are associated with significant limitations as they lack critical enzyme function such as CYP and transporter activity.

The HepaRG™ cell type (www.heparg.com) is an appealing alternative as it addresses a number of these limitations. It is a bi-potent hepatic progenitor cell line derived from an hepatocholangiocarcinoma and differentiates into hepatocyte-like and biliary-like cells. The cells are received in cryopreserved format as a terminally differentiated co-culture and maintain many key primary human hepatocyte characteristics including CYP, MAO and specific transporter activity.

Oxygen consumption can be assessed with HepaRG™ cells using the Mito-ID® Extracellular O2 Sensor Kit (High Sensitivity). Analysis is conducted on a standard 96-well plate format and facilitates a detailed analysis of the mitochondrial function. These cells are a superior model for the assessment of drug-induced mitochondrial dysfunction as they offer the capability to assess CYP and transporter mediated toxicity which is not possible with the standard alternative cell lines.

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