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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
In vivo reprogramming as a new approach to cardiac regenerative therapy
Taketaro Sadahiro1, Masaki Ieda1
1Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba City, Ibaraki 305-8575, Japan.
Abstract:
Cardiovascular diseases are a common cause of death worldwide. Adult cardiomyocytes have limited regenerative capacity after injury, and there is growing interest in cardiac regeneration as a new therapeutic strategy. There are several limitations of induced pluripotent stem cell-based transplantation therapy with respect to efficiency and risks of tumorigenesis. Direct reprogramming enables the conversion of terminally differentiated cells into target cell types using defined factors. In most cardiac diseases, activated fibroblasts proliferate in the damaged heart and contribute to the progression of heart failure. In vivo cardiac reprogramming, in which resident cardiac fibroblasts are converted into cardiomyocytes in situ, is expected to become a new cardiac regenerative therapy. Indeed, we and other groups have demonstrated that in vivo reprogramming improves cardiac function and reduces fibrosis after myocardial infarction. In this review, we summarize recent discoveries and developments related to in vivo reprogramming. In addition, issues that need to be resolved for clinical application are described.
Insights
Direct reprogramming converts fibroblasts into cardiomyocytes within the heart, offering a promising new therapy for cardiac regeneration after injury. This approach improves heart function and reduces scarring, overcoming limitations of stem cell therapies.
Area of Science:
- Cardiovascular biology and regenerative medicine.
- Cellular reprogramming and tissue engineering.
Background:
- Cardiovascular diseases are a leading global cause of mortality.
- Adult cardiomyocyte regeneration is limited, driving research into new therapeutic strategies.
- Stem cell therapies face challenges like efficiency and tumorigenesis.
Purpose of the Study:
- To review recent advancements in in vivo cardiac reprogramming.
- To explore the potential of direct reprogramming for cardiac regeneration.
- To identify challenges for clinical application of this therapy.
Main Methods:
- Direct reprogramming of terminally differentiated cells into desired cell types using defined factors.
- In vivo reprogramming of resident cardiac fibroblasts into cardiomyocytes within the damaged heart.
- Review of existing research and experimental findings on in vivo reprogramming.
Main Results:
- In vivo reprogramming has been shown to improve cardiac function post-myocardial infarction.
- This method effectively reduces fibrosis in damaged heart tissue.
- Fibroblast proliferation contributes to heart failure progression.
Conclusions:
- In vivo cardiac reprogramming is a promising regenerative therapy for heart disease.
- It offers an alternative to stem cell transplantation with potentially fewer risks.
- Further research is needed to address clinical application challenges.
