Year 1

The efficacy of the exosomes generated from the iPSC-derived cardiomyocytes has been demonstrated in both in vitro system consisting of autologous iPSC-derived cardiomyocytes (iCMs) and in in vivo murine myocardial injury model. The 2 major findings are the following:

1. Hypoxic iPSC-cardiovascular derivatives (cardiomyocytes, endothelial cells, and mesenchymal stem cells) all generate higher quantity and more efficacious exosomes as assessed by their restorative effects in both in vitro iCM and in vivo murine myocardial injury models. 

2.  Potential underlying mechanism of the exosomes has been elucidated. miR 106a-363 cluster in the X-chromose, consisting of miR 106a, 18b, 20b, 19b, 92a, and 363, has demonstrated similar restorative effects in the injured iCMs and murine myocardium. The exosome- and miR-treated iCMs have demonstrated improved contractile and electrophysiological properties. The exosomes from hypoxic iCMs demonstrated significant improvement in the function and viability of the injured murine myocardium. 

Currently, Discovery Quest Award application is submitted to confirm these findings in porcine myocardial injury model in preparation for FDA pre-pre-IND application.