Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration

John H. Werner, John H. Rosenberg, John Y. Um, Michael J. Moulton, Devendra K. Agrawal

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-β enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

Original languageEnglish (US)
JournalTranslational Research
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cardiac Myocytes
Regeneration
Fibroblasts
Tissue
MicroRNAs
Transcription Factors
Stem cells
Vascular Endothelial Growth Factor A
Induced Pluripotent Stem Cells
Cells
Modulation
Wounds and Injuries
Molecules
Myocardial Infarction
Cell Line
Therapeutics

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Biochemistry, medical

Cite this

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration. / Werner, John H.; Rosenberg, John H.; Um, John Y.; Moulton, Michael J.; Agrawal, Devendra K.

In: Translational Research, 01.01.2018.

Research output: Contribution to journalArticle

@article{fb4de1aae6b942b8bfd6ed6f3abdcf65,
title = "Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration",
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. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-β enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.",
author = "Werner, {John H.} and Rosenberg, {John H.} and Um, {John Y.} and Moulton, {Michael J.} and Agrawal, {Devendra K.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.trsl.2018.07.012",
language = "English (US)",
journal = "Translational Research",
issn = "1931-5244",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration

AU - Werner, John H.

AU - Rosenberg, John H.

AU - Um, John Y.

AU - Moulton, Michael J.

AU - Agrawal, Devendra K.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-β enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

AB - 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. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-β enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

UR - http://www.scopus.com/inward/record.url?scp=85052729472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052729472&partnerID=8YFLogxK

U2 - 10.1016/j.trsl.2018.07.012

DO - 10.1016/j.trsl.2018.07.012

M3 - Article

JO - Translational Research

JF - Translational Research

SN - 1931-5244

ER -