In Vitro Hepatotoxicity Profiling Using Corning? Epic? Label-Free Technology with Primary Hepatocytes, HepG2 Cells, and Corning HepatoCells

To reduce time, expenses and resources in drug discovery, in vitro toxicity assays are used to detect adverse drug effects in earlier phases of drug development. In recent years, in vitro studies with primary human isolated hepatocytes have replaced animal models as the gold standard for liver toxicity studies, as they provide more accurate and less costly testing than animal models. However, primary human hepatocytes are available in limited supply and can exhibit variability between donor samples. Although cell lines, such as HepG2 cells, have been used to overcome these limitations, HepG2 cells display expression of drug-metabolizing enzymes that significantly differs from primary hepatocytes. Corning? HepatoCells are immortalized cryopreserved cells, derived from primary human hepatocytes that are consistent lot-to-lot and display primary hepatocyte characteristics, such as robust CYP3A4, 1A2, and 2B6 fold induction similar to primary hepatocytes. In conventional in vitro cytotoxocity assays, specific cytotoxic indicators, such as ATP depletion, must be measured, but the mechanisms of chemical injury can be diverse, and therefore several different indicators must be monitored. Additionally, the use of fluorescent or luminescent dyes, or radiolabeled compounds can introduce variables into the assay that are not replicated in vivo. Label-free dynamic mass redistribution (DMR) assays using Corning Epic technology offer an alternative approach, capturing the cell signaling activity that occurs upon drug exposure in a single time-resolved measurement. In this study, primary hepatocytes, HepG2 cells, and HepatoCells were assayed with known hepatotoxins using the Corning Epic BT reader, demonstrating the ability of the technology to detect cytotoxic responses, and comparing the responses between the three cell types.