Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage

Mari Isomi, Taketaro Sadahiro, Ryo Fujita, Yuto Abe, Yu Yamada, Tatsuya Akiyama, Hiroaki Mizukami, Tsugumine Shu, Keiichi Fukuda, Masaki Ieda

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume560
DOIs
Publication statusPublished - 2021 Jun 30
Externally publishedYes

Keywords

  • Cardiac regeneration
  • Fibroblast
  • Myocardial infarction
  • Reprogramming
  • Sendai virus vector

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage'. Together they form a unique fingerprint.

Cite this