Direct cardiac reprogramming

A novel approach for heart regeneration

Hidenori Tani, Taketaro Sadahiro, Masaki Ieda

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field.

Original languageEnglish
Article number2629
JournalInternational Journal of Molecular Sciences
Volume19
Issue number9
DOIs
Publication statusPublished - 2018 Sep 5
Externally publishedYes

Fingerprint

fibroblasts
viruses
Fibroblasts
regeneration
Viruses
Cardiac Myocytes
Sendai virus
Regeneration
myocardial infarction
fibrosis
scars
Transcription factors
muscles
MicroRNAs
death
genes
mice
Muscle
Tumors
therapy

Keywords

  • Cardiac regeneration
  • Cardiomyocytes
  • Direct reprogramming
  • Fibroblasts
  • Gene therapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Direct cardiac reprogramming : A novel approach for heart regeneration. / Tani, Hidenori; Sadahiro, Taketaro; Ieda, Masaki.

In: International Journal of Molecular Sciences, Vol. 19, No. 9, 2629, 05.09.2018.

Research output: Contribution to journalReview article

Tani, Hidenori ; Sadahiro, Taketaro ; Ieda, Masaki. / Direct cardiac reprogramming : A novel approach for heart regeneration. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 9.
@article{aca8e34b37344aa9b16580b77ae2684b,
title = "Direct cardiac reprogramming: A novel approach for heart regeneration",
abstract = "Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field.",
keywords = "Cardiac regeneration, Cardiomyocytes, Direct reprogramming, Fibroblasts, Gene therapy",
author = "Hidenori Tani and Taketaro Sadahiro and Masaki Ieda",
year = "2018",
month = "9",
day = "5",
doi = "10.3390/ijms19092629",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Direct cardiac reprogramming

T2 - A novel approach for heart regeneration

AU - Tani, Hidenori

AU - Sadahiro, Taketaro

AU - Ieda, Masaki

PY - 2018/9/5

Y1 - 2018/9/5

N2 - Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field.

AB - Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field.

KW - Cardiac regeneration

KW - Cardiomyocytes

KW - Direct reprogramming

KW - Fibroblasts

KW - Gene therapy

UR - http://www.scopus.com/inward/record.url?scp=85053076378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053076378&partnerID=8YFLogxK

U2 - 10.3390/ijms19092629

DO - 10.3390/ijms19092629

M3 - Review article

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 9

M1 - 2629

ER -