Abstract 10466: In vivo Reprogramming of Murine Cardiac Fibroblasts into Induced Cardiomyocytes
Heart failure affects millions worldwide and is a progressive disease. The human heart has limited endogenous regenerative capacity and is thus a target for novel regenerative medicine approaches. Cardiac fibroblasts comprise approximately 50% of cells in the mammalian heart and contribute to scar formation upon cardiac damage. Our recent report showing direct reprogramming of cardiac fibroblasts into cardiomyocyte-like cells by defined factors in vitro raises the possibility that endogenous cardiac fibroblasts could serve as a potential source of new cardiomyocytes for regenerative therapy. Here, we use genetic lineage-tracing to show that resident cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in the murine heart by local delivery of Gata4, Mef2c, Tbx5 (GMT) after coronary ligation. In vivo induced cardiomyocytes became bi-nucleated and assembled sarcomeres. Analysis of single cells revealed ventricular cardiomyoctye-like action potentials and gap junctions, necessary for electrical coupling. In vivo delivery of GMT attenuated infarct size and cardiac dysfunction 3 months after coronary ligation. These results indicate that a significant fraction of endogenous cardiac fibroblasts can be diverted to generate new cardiomyocytes and that introduction of cardiac reprogramming factors into cardiac fibroblasts in vivo can improve cardiac function after myocardial infarction.
- © 2011 by American Heart Association, Inc.