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ligation. Induced cardiomyocytes became bi-nucleate, assembled sarcomeres and had
cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-
like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In
vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3
months after coronary ligation. Delivery of the pro-angiogenic and fibroblast activating peptide,
Thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac
function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into
cardiomyocyte-like cells in their native environment for potential regenerative purposes.
Keywords
Cellular reprogramming; Cardiomyocyte; Cardiac fibroblast; Thymosin β4
Heart failure affects over 14 million people worldwide and is a leading cause of death in
adults and in children. Because postnatal cardiomyocytes (CMs) have little or no
Correspondence: Deepak Srivastava, Gladstone Institute of Cardiovascular Disease,1650 Owens Street, San Francisco, CA 94158,
USA, Phone:[phone], Fax: [phone], ******@.
AUTHOR CONTRIBUTION
. designed, supervised and performed the experiments. . performed all surgeries, echoes and ECGs, and contributed to tissue
sectioning and sample preparation. . performed all cellular electrophysiology experiments. . quantified scar size and induced
cardiomyoyctes and helped with mouse colony maintenance. . hel