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- Title
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes.
- Authors
Qian, Li; Huang, Yu; Spencer, C Ian; Foley, Amy; Vedantham, Vasanth; Liu, Lei; Conway, Simon J; Fu, Ji-dong; Srivastava, Deepak
- Abstract
The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts,which represent 50%of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here we use genetic lineage tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became binucleate, 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 b4, 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.
- Publication
Nature, 2012, Vol 485, Issue 7400, p593
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature11044