Research Project
8619264
DESCRIPTION (provided by applicant): Hepatotoxicity is a leading cause of drug adverse events and clinical trial failure. The current gold standard for preclinical detection of hepatotoxicity involves assaying primary hepatocytes, but the inability to obtain large samples of such cells and resulting concerns about batch-to-batch variability limit their use in drug screening. In comparison, induced pluripotent stem cells (iPSCs) can in principle provide a replenish able supply of hepatocytes, which would enable extensive screening on a single stem cell line or across cell lines to evaluate patient-specific responses. However, it is expensive and time-consuming to grow stem cells or their progeny, thus as with cell-based assays in general, successful application of these cells for high-throughput drug screening requires miniaturization. Miniaturization reduces the number of cells required thereby increasing throughput per batch of differentiated hepatocytes, and it also decreases costs through reduced usage of expensive reagents. To address this issue, Euveda Biosciences has developed a novel cell-based assay platform based on microfluidic technology that reduces assay sample volumes by orders of magnitude compared to multiwell plates while improving fluid handling accuracy. In this Phase I project, we will combine the advantages of iPSC-derived cells and our miniaturized cell-based assay technology to create a more predictive, high-throughput hepatotoxicity screening platform. Successful completion of this project would demonstrate proof-of-principle that iPSC-derived hepatocytes maintain their viability and functionality in our microfluidic chip and display relevant drug responses. We envision a subsequent Phase II project primarily focused on validating a large set of iPSC-derived hepatocyte cell lines with representative genetic backgrounds for use in the platform, which would enable drug response variability in the human population to be modeled. Together, the chips and cells would be an attractive product to academic and industry pharmaceutical researchers that can dramatically improve the safety profile of compounds advanced to clinical trials.
