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Updated: Aug 31, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
The heart of cardiac reprogramming: The cardiac fibroblasts
1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC 27599, USA.
Insights
Direct cardiac reprogramming converts cardiac fibroblasts into functional cardiomyocytes, offering a promising strategy to repair heart tissue after myocardial infarction (MI) and improve cardiac function.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Molecular Cardiology
Background:
- Cardiovascular disease (CVD) is the leading global cause of mortality.
- Myocardial infarction (MI) is a major contributor to CVD, causing irreversible myocardial remodeling and cardiomyocyte loss.
- Current therapies for MI manage decline but do not restore cardiac function.
Purpose of the Study:
- To review direct cardiac reprogramming as a therapeutic strategy for repairing injured cardiac tissue.
- To describe methods for in vivo reprogramming of cardiac fibroblasts (CFs) into cardiomyocyte-like cells (iCMs).
- To highlight the potential of iCMs in restoring cardiac function post-MI.
Main Methods:
- Ectopic expression of transcription factors, microRNAs, or small molecules to induce reprogramming.
- Generation of induced cardiomyocyte-like cells (iCMs) from cardiac fibroblasts (CFs).
- In vivo induction of iCMs following myocardial infarction (MI) in preclinical models.
Main Results:
- Reprogrammed iCMs exhibit molecular, structural, and functional characteristics of endogenous cardiomyocytes.
- In vivo induction of iCMs significantly reduces fibrotic cardiac remodeling after MI.
- Improved cardiac function is observed following iCM generation in MI models.
Conclusions:
- Direct cardiac reprogramming is a viable therapeutic approach for repairing damaged heart tissue post-MI.
- Further research aims to enhance reprogramming efficiency for clinical translation.
- This strategy holds promise for restoring cardiac function and mitigating adverse remodeling.
Abstract:
Cardiovascular disease is the leading cause of death worldwide, outpacing pulmonary disease, infectious disease, and all forms of cancer. Myocardial infarction (MI) dominates cardiovascular disease, contributing to four out of five cardiovascular related deaths. Following MI, patients suffer adverse and irreversible myocardial remodeling associated with cardiomyocyte loss and infiltration of fibrotic scar tissue. Current therapies following MI only mitigate the cardiac physiological decline rather than restore damaged myocardium function. Direct cardiac reprogramming is one strategy that has promise in repairing injured cardiac tissue by generating new, functional cardiomyocytes from cardiac fibroblasts (CFs). With the ectopic expression of transcription factors, microRNAs, and small molecules, CFs can be reprogrammed into cardiomyocyte-like cells (iCMs) that display molecular signatures, structures, and contraction abilities similar to endogenous cardiomyocytes. The in vivo induction of iCMs following MI leads to significant reduction in fibrotic cardiac remodeling and improved heart function, indicating reprogramming is a viable option for repairing damaged heart tissue. Recent work has illustrated different methods to understand the mechanisms driving reprogramming, in an effort to improve the efficiency of iCM generation and create an approach translational into clinic. This review will provide an overview of CFs and describe different in vivo reprogramming methods.
