Recent advances and future prospects in direct cardiac reprogramming

Nat Cardiovasc Res. 2023 Dec;2(12):1148-1158. doi: 10.1038/s44161-023-00377-w. Epub 2023 Dec 11.

Abstract

Cardiovascular disease remains a leading cause of death worldwide despite important advances in modern medical and surgical therapies. As human adult cardiomyocytes have limited regenerative ability, cardiomyocytes lost after myocardial infarction are replaced by fibrotic scar tissue, leading to cardiac dysfunction and heart failure. To replace lost cardiomyocytes, a promising approach is direct cardiac reprogramming, in which cardiac fibroblasts are transdifferentiated into induced cardiomyocyte-like cells (iCMs). Here we review cardiac reprogramming cocktails (including transcription factors, microRNAs and small molecules) that mediate iCM generation. We also highlight mechanistic studies exploring the barriers to and facilitators of this process. We then review recent progress in iCM reprogramming, with a focus on single-cell '-omics' research. Finally, we discuss obstacles to clinical application.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Transdifferentiation
  • Cellular Reprogramming*
  • Fibroblasts
  • Humans
  • MicroRNAs / genetics
  • Myocytes, Cardiac* / metabolism
  • Regeneration / physiology
  • Regenerative Medicine / methods
  • Regenerative Medicine / trends
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • MicroRNAs
  • Transcription Factors