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Updated: Oct 30, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart
Emma Adams1, Rachel McCloy1, Ashley Jordan1
1Pharmacy and Biomolecular Science, Liverpool John Moores University, Liverpool L3 3AF, UK.
Insights
Scientists are exploring direct reprogramming to regenerate heart muscle after myocardial infarction. This approach aims to convert scar tissue into new heart cells, offering hope for treating heart failure.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Developmental Biology
Background:
- Coronary heart disease is a major cause of death.
- Survivors of myocardial infarction face high risk of heart failure due to myocardial fibrosis.
- Current treatments do not fully address fibrotic remodeling post-infarction.
Purpose of the Study:
- To review mechanisms of embryonic cardiovascular development.
- To establish a framework for understanding direct reprogramming of cardiac cells.
- To explore the potential for myocardial regeneration via direct reprogramming.
Main Methods:
- Review of embryonic cell fate specification in cardiovascular development.
- Analysis of transcription factor networks, microRNAs, and epigenetic modifiers in cell reprogramming.
- Examination of direct transdifferentiation of cardiac fibroblasts to cardiomyocytes.
Main Results:
- Embryonic development provides insights into cell fate specification.
- Direct reprogramming can bypass induced pluripotency, enabling cell transdifferentiation.
- A specific network of transcription factors, akin to embryonic cardiac progenitors, facilitates cardiac fibroblast to cardiomyocyte transdifferentiation.
Conclusions:
- Direct reprogramming offers a potential strategy for myocardial regeneration.
- Targeting cardiac fibroblasts in post-infarct scar tissue could reverse heart failure.
- Further research into reprogramming networks may lead to novel cardiac therapies.
Abstract:
Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue.
