Direct Cardiac Reprogramming for Cardiovascular Regeneration and Differentiation

Keio J Med. 2020 Sep 25;69(3):49-58. doi: 10.2302/kjm.2019-0008-OA. Epub 2020 Jan 9.


Cardiovascular disease is the leading cause of death worldwide. Cardiomyocytes have limited regenerative capacity; consequently, regenerative therapies are in high demand. There are currently several potential strategies for heart regeneration, with one approach involving in situ generation of new cardiomyocytes from endogenous cell sources. Direct cardiac reprogramming has emerged as a novel therapeutic approach to regenerating the damaged heart by directly converting endogenous cardiac fibroblasts into cardiomyocyte-like cells. Following our first report of direct cardiac reprogramming, significant advances have elucidated the molecular mechanisms associated with cardiac reprogramming. These advances have also improved cardiac-reprogramming efficiency by enabling direct in vivo cardiac reprogramming. Moreover, progress has been made in cardiac reprogramming of human fibroblasts. Although basic research has supported substantial progress in this field, numerous challenges remain in terms of clinical application. Here, we review the current state of cardiac reprogramming as a new technology for understanding and treating cardiovascular diseases.

Keywords: cardiomyocytes; direct reprogramming; fibroblasts; regeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy*
  • Cell Differentiation
  • Cellular Reprogramming / genetics*
  • Disease Models, Animal
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • GATA4 Transcription Factor / genetics
  • GATA4 Transcription Factor / metabolism
  • Gene Expression Regulation*
  • Humans
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / metabolism
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Regeneration / genetics*
  • Regenerative Medicine / methods
  • Regenerative Medicine / trends
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Translational Medical Research / methods
  • Translational Medical Research / trends


  • GATA4 Transcription Factor
  • Gata4 protein, mouse
  • MEF2 Transcription Factors
  • Mef2c protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor 5