Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 560, Issue -, Pages 87-92Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.04.121
Keywords
Reprogramming; Sendai virus vector; Fibroblast; Cardiac regeneration; Myocardial infarction
Categories
Funding
- Practical Research Project for Rare/Intractable Diseases [JP20ek0109305]
- Research Center Network for Realization of Regenerative Medicine [JP20bm0704030]
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science [19K22613, 19K17550]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [19K17550, 19K22613] Funding Source: KAKEN
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Adult hearts have limited regenerative capacity, but direct reprogramming of cardiac fibroblasts into induced cardiomyocytes with GMT may have significant potential for cardiac repair. Studies have shown that SeV-GMT reprogramming in mouse hearts after acute MI can improve cardiac function.
Adult hearts have limited regenerative capacity. Hence, after acute myocardial infarction (MI), dead myocardial tissues are digested by immune cells and replaced by fibrosis, leading to ventricular remodeling and heart failure at the chronic stage. Direct reprogramming of the cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) with cardiac transcription factors, including Gata4, Mef2c, and Tbx5 (GMT), may have significant potential for cardiac repair. Sendai virus (SeV) vectors expressing GMT have been reported to reprogram the mouse cardiac fibroblasts into iCMs without any risk of insertional mutagenesis. In vivo reprogramming improved the cardiac function after acute MI in immunodeficient mice. However, it is unknown whether the newly generated iCMs could exist in infarct hearts for a prolonged period and SeV-GMT can improve cardiac function after MI at the chronic stage in immunocompetent mice. Here, we show that SeV vectors efficiently infect CFs in vivo and reprogram them into iCMs, which existed for at least four weeks after MI, in fibroblast-linage tracing mice. Moreover, SeV-GMT improved cardiac function and reduced fibrosis and collagen I expression at 12 weeks after MI in immunocompetent mice. Thus, direct cardiac reprogramming with SeV vectors could be a promising therapy for MI. (c) 2021 Elsevier Inc. All rights reserved.
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