Electrical Function of Human Pluripotent Stem Cell-Derived Cardiomyocyte Grafts

Human pluripotent stem cells (hPSCs) have a number of potential advantages for use in myocardial infarct repair, including a tremendous capacity for expansion in the undifferentiated state followed by the ability to differentiate into phenotypically unambiguous cardiomyocytes. Our group has contributed to the development of efficient, reliable protocols to generate large quantities of hPSC-derived cardiomyocytes (hPSC-CMs), and we have shown that the transplantation of hPSC-CMs results in the partial remuscularization of injured hearts in multiple preclinical models. Despite this, a number of important challenges remain, including concerns about the immature and heterogeneous electrophysiological phenotype of hESC-derived cardiomyocytes, the ability of these cells to undergo appropriate electromechanical integration following transplantation, and the risk of graft-related arrhythmogenesis. In this presentation, I will describe our group's recent efforts to understand and improve the electrical function of hPSC-CM grafts in injured hearts, including 1) the development of improved protocols to promote the electrophysiological maturation of hPSC-CMs in vitro, 2) new optical mapping methods to study hPSC-CM electrical behavior in vivo, and 3) transplantation studies in a more relevant porcine infarct model.