Three Dimensional Hepatotoxicity Screening using Corning? HepatoCells, the Spheroid Microplate and the SCREEN-WELL? Hepatotoxicity library

Having the right model for drug screening is essential for predicting compounds that may cause drug-induced liver injury. Three dimensional (3D) models offer significant improvements over traditional two dimensional monolayer cell culture in terms of maintaining morphological and functional characteristics of tissue, and may provide a better representation of in vitro drug toxicity1. Here we demonstrate how Corning HepatoCells, an immortalized alternative to primary human hepatocytes, in conjunction with Corning Spheroid Microplates can be a utilized for a 3D drug screen to discover potential hepatotoxins. Hepatospheres formed using Corning HepatoCells were compared to spheroids formed using alternative hepatocyte-like models. Cell viability, urea and albumin were measured to assess hepatotoxicity after exposure to the SCREEN-WELL Hepatotoxicity library from Enzo Life Sciences, a library consisting of 238 compounds with a variety of structurally and mechanistically different compound classes, as well as nontoxic controls. Selected hits identified in the 3D screen, which significantly reduced cell viability of the hepatospheres, were then assessed in a dose-dependent manner for potency analysis. These results demonstrate that Corning HepatoCells, together with Corning Spheroid Microplates, are powerful tools that can be used for reliable and reproducible 3D hepatotoxicity screening.