Albert Wong1, Jonathan Weinreich1, Alexandra Wolff1, Hilary Sherman2, Hannah J. Gitschier2, and David H. Randle Ph.D2
1 Enzo Life Sciences, Farmingdale, NY, USA
2 Corning Incorporated, Life Sciences, Kennebunk, Maine USA
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Having the right model for drug screening is essential for predicting which compounds 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 utilized for a 3D drug screen to discover potential hepatotoxins. Hepatospheres formed using Corning HepatoCells were compared to spheroids formed using alternative immortalized hepatocyte cells. Cell viability, urea, and albumin were used to assess hepatotoxicity of the hepatospheres 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.