Direct cardiac reprogramming

progress and challenges in basic biology and clinical applications

Taketaro Sadahiro, Shinya Yamanaka, Masaki Ieda

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The discovery of induced pluripotent stem cells changed the field of regenerative medicine and inspired the technological development of direct reprogramming or the process by which one cell type is directly converted into another without reverting a stem cell state by overexpressing lineage-specific factors. Indeed, direct reprogramming has proven sufficient in yielding a diverse range of cell types from fibroblasts, including neurons, cardiomyocytes, endothelial cells, hematopoietic stem/progenitor cells, and hepatocytes. These studies revealed that somatic cells are more plastic than anticipated, and that transcription factors, microRNAs, epigenetic factors, secreted molecules, as well as the cellular microenvironment are all important for cell fate specification. With respect to the field of cardiology, the cardiac reprogramming presents as a novel method to regenerate damaged myocardium by directly converting endogenous cardiac fibroblasts into induced cardiomyocyte-like cells in situ. The first in vivo cardiac reprogramming reports were promising to repair infarcted hearts; however, the low induction efficiency of fully reprogrammed, functional induced cardiomyocyte-like cells has become a major challenge and hampered our understanding of the reprogramming process. Nevertheless, recent studies have identified several critical factors that may affect the efficiency and quality of cardiac induction and have provided new insights into the mechanisms of cardiac reprogramming. Here, we review the progress in direct reprogramming research and discuss the perspectives and challenges of this nascent technology in basic biology and clinical applications.

Original languageEnglish
Pages (from-to)1378-1391
Number of pages14
JournalCirculation Research
Volume116
Issue number8
DOIs
Publication statusPublished - 2015 Apr 10

Fingerprint

Cardiac Myocytes
Hematopoietic Stem Cells
Fibroblasts
Cellular Microenvironment
Induced Pluripotent Stem Cells
Regenerative Medicine
Cardiology
MicroRNAs
Epigenomics
Plastics
Hepatocytes
Myocardium
Transcription Factors
Stem Cells
Endothelial Cells
Technology
Neurons
Research

Keywords

  • fibroblasts
  • induced pluripotent stem cells
  • myocytes, cardiac

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Direct cardiac reprogramming : progress and challenges in basic biology and clinical applications. / Sadahiro, Taketaro; Yamanaka, Shinya; Ieda, Masaki.

In: Circulation Research, Vol. 116, No. 8, 10.04.2015, p. 1378-1391.

Research output: Contribution to journalArticle

Sadahiro, Taketaro ; Yamanaka, Shinya ; Ieda, Masaki. / Direct cardiac reprogramming : progress and challenges in basic biology and clinical applications. In: Circulation Research. 2015 ; Vol. 116, No. 8. pp. 1378-1391.
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