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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-The Future of Cardiac Regeneration?
Stefanie A Doppler1, Marcus-André Deutsch2, Rüdiger Lange3,4
1Division of Experimental Surgery, Department of Cardiovascular Surgery, Deutsches Herzzentrum München, Technische Universität München (TUM), Munich 80636, Germany. doppler@dhm.mhn.de.
Insights
Direct reprogramming offers a promising regenerative therapy for congestive heart failure (CHF) by converting scar cells into heart muscle. This approach bypasses limitations of heart transplantation for end-stage CHF.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Biology
Background:
- Heart transplantation is the only curative option for end-stage congestive heart failure (CHF), but donor heart scarcity and graft issues limit its use.
- Current regenerative strategies like stem cell therapy have shown inconsistent results in clinical trials for CHF.
- Developing alternative treatments is crucial due to the poor prognosis of advanced CHF.
Purpose of the Study:
- To review strategies for direct cardiac reprogramming, a novel regenerative approach for CHF.
- To explore the use of transcription factors, microRNAs, and small molecules in direct reprogramming.
- To assess the potential of generating functional cardiomyogenic cells for cardiac repair.
Main Methods:
- Review of pre-clinical research on direct lineage conversion of fibroblasts into cardiomyocytes.
- Analysis of studies utilizing transcription factors, microRNAs, and small molecules for reprogramming.
- Evaluation of methods for efficient generation of cardiomyogenic cells.
Main Results:
- Direct reprogramming shows promise in converting scar fibroblasts into functional myocardium.
- Various molecular tools, including transcription factors, microRNAs, and small molecules, are being investigated.
- Pre-clinical data suggests potential for generating cardiomyogenic cells for regenerative purposes.
Conclusions:
- Direct reprogramming represents a highly promising strategy for treating end-stage congestive heart failure.
- This approach offers an alternative to heart transplantation by regenerating cardiac tissue.
- Further research into molecular mechanisms and clinical translation is warranted.
Abstract:
Today, the only available curative therapy for end stage congestive heart failure (CHF) is heart transplantation. This therapeutic option is strongly limited by declining numbers of available donor hearts and by restricted long-term performance of the transplanted graft. The disastrous prognosis for CHF with its restricted therapeutic options has led scientists to develop different concepts of alternative regenerative treatment strategies including stem cell transplantation or stimulating cell proliferation of different cardiac cell types in situ. However, first clinical trials with overall inconsistent results were not encouraging, particularly in terms of functional outcome. Among other approaches, very promising ongoing pre-clinical research focuses on direct lineage conversion of scar fibroblasts into functional myocardium, termed "direct reprogramming" or "transdifferentiation." This review seeks to summarize strategies for direct cardiac reprogramming including the application of different sets of transcription factors, microRNAs, and small molecules for an efficient generation of cardiomyogenic cells for regenerative purposes.
