In vivo Direct Reprogramming of Fibroblasts into Cardiomyocyte-Like Cells Though Inhibition of HDACs and TGF-β Pathway

Background: Substantial progress has been recently achieved that direct lineage reprogramming induced by small molecule compounds was possible either in vitro or in vivo, which provided a promising cellular strategy for regenerative therapy. Method: A combination of an inhibitor of HDACs, valproic acid (V) and an inhibitor of TGF-β pathway, tranilast (T) were applied to identify the conversation of fibroblasts into induced cardiomyocyte-like cells (iCMs) in situ in mice with myocardial infarction. Result: We found that the combination of two small molecules, V&T could reprogram cardiac fibroblasts into iCMs in vivo, which were co-labeled with vimentin and a-actin 4 weeks after myocardial infarction; while, the phenomenon was found neither in mice with non-myocardial infarction nor in mice with myocardial infarction induced only by physiological saline. And furthermore, these iCMs resembled mouse native cardiomyocytes regarding their specific molecular phenotypes: a-MHC, c-TnT, connexin-43. However, the early marker of progenitor cells prior to cardiac differentiation, Mesp1, wasn’t detected in the infarcted and border zone. Conclusion: HDACs and TGF-β inhibitors jointly could achieve direct cardiac reprogramming from cardiac fibroblasts in vivo, without establishing a pluripotent state and thus, provide a new important therapeutic application for cardiac regeneration. In vivo Direct Reprogramming of Fibroblasts into Cardiomyocyte-Like Cells Through Inhibition of HDACs and TGF-β Pathway Hua Li1, Junbo Ge2,3, and Gang Pei1,4* 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China 3Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 4School of Life Science and Technology, Tongji University, Shanghai 200092, China *Corresponding author: Gang Pei, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, Tel: +86-21-54921371; E-mail: [email protected] Received January 10, 2017; Accepted January 20, 2017; Published January 27, 2017 Citation: Hua Li, Junbo Ge, Gang Pei (2017) In vivo Direct Reprogramming of Fibroblasts into Cardiomyocyte-Like Cells Through Inhibition of HDACs and TGF-β Pathway. J Stem Cell Res Ther 7: 373. doi: 10.4172/2157-7633.1000373 Copyright: © 2017 Hua Li, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.