Cardiomyocyte Proliferation for Therapeutic Regeneration
Purpose of Review
Current pharmacologic treatments for cardiovascular disease do not correct the underlying cellular defect, the loss of cardiomyocytes. With recent advancements in cardiac regenerative approaches, the induction of endogenous mature cardiomyocyte proliferation has emerged as a new possibility. Here, we review progress made toward the regeneration of cardiac tissue in the mammalian heart through the stimulation of mature cardiomyocyte renewal.
The targeting of several developmental and signaling pathways has been shown to stimulate cell cycle re-entry in mature cardiomyocytes. In animal models of cardiac regeneration, various strategies have been used to target these pathways to stimulate cardiomyocyte renewal and have relied on the delivery of signaling factors via systemic delivery, epicardial patches, or direct intramyocardial injection. Gene therapy techniques involving the viral delivery of transgenes by using adenoviral or adeno-associated viral vectors have been used to successfully target cardiac gene expression. The delivery of nucleic acids in the form of anti-microRNAs and microRNA mimetics has also been shown to be effective in stimulating cardiomyocyte renewal.
As the field of cardiac regeneration continues to progress, an important ongoing challenge in developing clinically translatable therapies is limiting the stimulation of growth pathways in non-cardiomyocytes.
KeywordsCardiomyocyte Regeneration Proliferation Cell cycle Heart failure Cardiovascular disease
We apologize to researchers whose work is not cited here because of space constraints. Nicole Stancel, PhD, ELS, of the Section of Scientific Publications at the Texas Heart Institute, provided editorial support.
Supported by the National Institutes of Health (DE 023177, HL 127717, HL 130804, and HL 118761 to J.F.M.), MacDonald Research Fund Award 16RDM001 (J.F.M.), and the Vivian L. Smith Foundation (J.F.M.). J.F.M. was supported by the LeDucq Foundation’s Transatlantic Networks of Excellence in Cardiovascular Research (14CVD01: “Defining the Genomic Topology of Atrial Fibrillation”).
Compliance with Ethical Standards
Conflict of Interest
John P. Leach and James F. Martin report a patent US9732345B2 issued.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human subjects performed by any of the authors.
All mouse procedures were performed in accordance with institutional and governmental guidelines and were approved by the Baylor College of Medicine Institutional Animal Care and Use Committee.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance
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