Abstract 18472: Enhancing the Therapeutic Potential of Induced Pluripotent Stem Cell Derived Cardiomyocytes Through Targeting the Hippo Signalling Pathway

Cell based therapy using stem cell derived cardiomyocytes, has emerged as a potential therapeutic approach for cardiac diseases such as myocardial infarction and heart failure. Induced pluripotent stem cells (iPSC) could be an ideal source of cardiomyocytes (iPS-CM). However, challenges facing this approach include the high number of viable cells needed to survive in pathological conditions. The Hippo signalling pathway is a key pathway involved in regulating cardiomyocyte proliferation and survival in both embryonic and adult hearts. In this study, we target the Hippo pathway to enhance the therapeutic potential of iPS-CM.Skin fibroblasts were reprogrammed to iPSC and then differentiated to cardiomyocytes. The Hippo pathway was modified by genetic ablation of Mst1, a major upstream regulator of the Hippo pathway, or by overexpressing YAP, the main downstream effector of the pathway. We found that genetic ablation of Mst1 leads to significantly increased reprogramming efficiency by 43.8±2.4%. iPSC lacking MST1 displayed increase proliferation (12±1.5% P