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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Direct reprogramming of fibroblasts into cardiomyocytes
Yueqiu Chen1,2, Ziying Yang1, Zhen-Ao Zhao3
1Institute for Cardiovascular Science & Department of Cardiovascular Surgery of The First Affiliated Hospital, Soochow University, 708 Renmin Road, Building 1, Room 1628, Suzhou, Jiangsu, 215007, China.
Insights
Reprogramming scar-forming myofibroblasts into cardiomyocyte-like cells offers a promising strategy for heart regeneration. This approach aims to reduce scar tissue and increase functional heart muscle cells after injury.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Cellular Reprogramming
Background:
- Cardiovascular diseases are the leading global cause of mortality.
- Limited regeneration capacity of adult cardiomyocytes hinders heart repair after myocardial infarction.
- Myofibroblasts dominate the infarct zone post-myocardial infarction.
Purpose of the Study:
- To explore the potential of directed cardiac reprogramming for heart regeneration.
- To summarize and compare advancements in reprogramming myofibroblasts into cardiomyocyte-like cells.
- To discuss clinical translation challenges for cardiac reprogramming strategies.
Main Methods:
- Review of studies utilizing transcription factors for myofibroblast reprogramming.
- Analysis of microRNAs and small molecules for optimizing cardiac reprogramming.
- Systematic comparison of different reprogramming approaches.
Main Results:
- Transcription factors were the initial drivers of myofibroblast-to-cardiomyocyte reprogramming.
- MicroRNAs and small molecules have shown significant potential in enhancing reprogramming efficiency.
- Directed reprogramming offers a dual benefit of scar reduction and cardiomyocyte generation.
Conclusions:
- Direct reprogramming of myofibroblasts presents a viable strategy for treating heart damage.
- Further research is needed to overcome challenges for clinical application.
- Optimizing reprogramming protocols with small molecules and miRNAs is crucial for therapeutic success.
Abstract:
Cardiovascular diseases are the leading causes of death in the world. The limited regenerative capacity of adult cardiomyocytes is the major barrier for heart regeneration. After myocardial infarction, myofibroblasts are the dominant cell type in the infarct zone. Therefore, it is a good idea to reprogram terminally differentiated myofibroblasts into cardiomyocyte-like cells directly, providing a good strategy to simultaneously reduce scar tissue and increase functional cardiomyocytes. Transcription factors were first identified to reprogram myofibroblasts into cardiomyocytes. Thereafter, microRNAs and/or small molecules showed great potential to optimize the reprogramming process. Here, we systemically summarize and compare the major progress in directed cardiac reprogramming including transcription factors and miRNAs, especially the small molecules. Furthermore, we discuss the challenges needed to be overcome to apply this strategy clinically.
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