Category: Assay Development and Screening
Drug induced liver injury (DILI) is one of the most cited causes of clinical drug attrition, and is often the reason for withdrawal of approved drugs from the market. More accurate in vitro toxicity assays are required to detect adverse drug effects in earlier phases of drug development. Three dimensional (3D) cell models have been shown to demonstrate the formation of functional bile canaliculi and have exhibited increased albumin secretion and CYP expression as well as stability for longer periods in culture compared with two dimensional (2D) cultures. Corning® HepatoCells are immortalized cells derived from primary human hepatocytes (PHH) that retain metabolic and enzymatic functionality of PHH but without the lot-to-lot variability and reliance on human donors of PHH. Here we demonstrate how Corning HepatoCells in conjunction with Corning Spheroid microplates can be utilized for a 3D drug screen to discover potential hepatotoxins by way of multiparameter high content screening (HCS) analyses. Specifically, lipid accumulation and mitochondrial membrane potential loss were examined after exposure to a variety of known hepatotoxic compounds. These results indicate that Corning HepatoCells, together with Corning spheroid microplates, are powerful tools for reliable and reproducible in vitro 3D hepatotoxicity screening to predict liver injury.
Audrey Bergeron– Applications Scientist, Corning Life Sciences, Kennebunk, ME