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Published on: September 3, 2020
Cardiac Regeneration After Myocardial Infarction: an Approachable Goal
Mauro Giacca1,2
1King's College London, British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine & Sciences, SE5 9NU London, United Kingdom. mauro.giacca@kcl.ac.uk.
Insights
Cardiac regeneration is now possible through stem cell therapy or stimulating the heart's own repair mechanisms. While promising, further research is needed for widespread clinical use in treating heart damage.
Area of Science:
- Cardiology
- Regenerative Medicine
- Stem Cell Biology
Background:
- Cardiac regeneration after myocardial infarction was considered unattainable.
- Previous clinical trials with adult stem cells yielded disappointing results.
- The heart was widely believed to be a post-mitotic organ with no regenerative capacity.
Purpose of the Study:
- To review recent advancements challenging the notion of the heart as an irreversibly post-mitotic organ.
- To explore current strategies for achieving cardiac regeneration.
- To assess the potential for clinical application of these regenerative approaches.
Main Methods:
- Generating new cardiomyocytes from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs).
- Administering generated cardiomyocytes as cell suspensions or in engineered myocardial tissues.
- Stimulating endogenous cardiomyocyte proliferation via gene or microRNA delivery.
Main Results:
- Successful cardiac regeneration demonstrated in large animal models using both cell-based and gene-based strategies.
- ESC/iPSC-derived cardiomyocytes can be used for cardiac repair.
- MicroRNA-based approaches show significant promise in enhancing endogenous repair.
Conclusions:
- Cardiac regeneration is achievable through multiple innovative strategies.
- Recent experimental successes in large animals provide strong evidence for feasibility.
- Technical challenges remain before widespread clinical translation can be realized.
Purpose Of Review:
Until recently, cardiac regeneration after myocardial infarction has remained a holy grail in cardiology. Failure of clinical trials using adult stem cells and scepticism about the actual existence of such cells has reinforced the notion that the heart is an irreversibly post-mitotic organ. Recent evidence has drastically challenged this conclusion.
Recent Findings:
Cardiac regeneration can successfully be obtained by at least two strategies. First, new cardiomyocytes can be generated from embryonic stem cells or induced pluripotent stem cells and administered to the heart either as cell suspensions or upon ex vivo generation of contractile myocardial tissue. Alternatively, the endogenous capacity of cardiomyocytes to proliferate can be stimulated by the delivery of individual genes or, more successfully, of selected microRNAs. Recent experimental success in large animals by both strategies now fuels the notion that cardiac regeneration is indeed possible. Several technical hurdles, however, still need to be addressed and solved before broad and successful clinical application is achieved.
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