Microfluidic Assay for Screening Vascular Cardiotoxicity

Abstract The overall objective of this study is to develop a novelpredictive in vitro platform for studying physiological responses of endothelium mediated human cardiomyocytes toxicity to therapeuticsThe proposed effort specifically responds to NHLBI Small Business Topics of Special Interest HLSA critical in vivo component lacking in conventional models used for cardiac toxicity is the absence of endothelial cells and perivascular cells in communication with cardiomyocytes thereby limiting realistic predictionsWe propose to develop and demonstrate iPSCs based microfluidic device and assay that will accurately reproduce the physiological conditions of vascular and cardiac tissue interactions observed in vivoPhase I will culminate with a clear demonstration of endothelium mediated toxicity screening with physiological relevant modulation of cardiomyocytes and endothelial cells caused by drug induced interactionsDuring Phase IIwe will expand the platform further with culture of perivascular cellsand perform toxicity screening with clinically relevant drugs followed by in vivo validationWe will also develop a framework for high throughput assays by integration with micro well platesA multi disciplinarypartnership with expertise in microfluidics cell based assaysiPSC based cardiomyocytesnative extracellular matricesregenerative medicine and cardiac toxicity with clinical relevance has been assembled to successfully meet the research objectivesThe end product will be commercialized to researchers in industry and academia engaged in drug discovery and drug deliveryThe developed assay will also have critical applications in basic researchwhere it can be used to identify molecular mechanisms and in drug discovery for development of therapeutics Project NarrativeThe overall objective of this study is to develop a novelpredictive in vitro platform for studying physiological responses of endothelium mediated human cardiomyocytes toxicity to therapeuticsThe end product will be commercialized to pharmaceutical firmsdrug research labs and universities non profit centers engaged in precision therapeuticsdrug discoveryand drug delivery