Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration

Translational Research : the Journal of Laboratory and Clinical Medicine
John H WernerDevendra K Agrawal

Abstract

Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector-driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR-1, miR-133, miR-208, and miR-499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. ...Continue Reading

Citations

Apr 17, 2020·Frontiers in Cardiovascular Medicine·Pim R R van GorpAntoine A F de Vries
Oct 22, 2020·International Journal of Molecular Sciences·Lin JiangYigang Wang
Feb 20, 2021·Journal of Cellular and Molecular Medicine·Su-Kiat ChuaKou-Gi Shyu
Jul 3, 2021·Journal of Cardiovascular Development and Disease·Emma AdamsIain M Dykes

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