In order to reduce the cost of bringing a new drug to market, drug candidates with a high probability for failure must be identified early in their development. The pharmaceutical industry employs in vitro liver models to screen new drugs for undesirable toxic metabolites and harmful drug-drug interactions. Primary human hepatocytes are the preferred model for assessing drug metabolism, hepatoxicity, drug-drug interactions, and CYP450 enzyme induction. However, the availability of fresh human hepatocytes is unpredictable, leading researchers to develop cryopreservation methods that enable long-term hepatocyte storage. Despite the advantages of this technique, 50% of hepatocytes lose their ability to attach to culture plates following cryopreservation. Unlike plated hepatocytes that remain viable for days to weeks, hepatocytes in suspension are only viable for a few hours;thus, non-plateable hepatocytes are limited in use to only short-term metabolic assays. Ultimately, this diminishes the available supply of fully functional hepatocytes, increasing costs for both hepatocyte suppliers and end users. Affinergy has identified peptide sequences that bind specifically to non- plateable cryopreserved hepatocytes. We will utilize these peptides to attach non-plateable hepatocytes to collagen-coated well plates. We expect that this attachment will reverse signaling cascades associated with """"""""detachment-induced cell death"""""""", ultimately giving the cells time to restore contact with the underlying collagen substrates.
