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Cardiomyocyte Proliferation for Therapeutic Regeneration

  • Regenerative Medicine (SM Wu, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

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.

Recent Findings

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.

Summary

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.

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Acknowledgments

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.

Funding

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”).

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Author notes

  1. John P. Leach

    Present address: Department of Medicine, Penn Center for Pulmonary Biology, Penn Cardiovascular Institute, Penn Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    John P. Leach & James F. Martin

  2. Cardiomyocyte Renewal Lab, Texas Heart Institute, 6770 Bertner Avenue, Houston, TX, 77030, USA

    James F. Martin

  3. Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    James F. Martin

  4. Cardiovascular Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    James F. Martin

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Correspondence to James F. Martin.

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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.

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This article is part of the Topical Collection on Regenerative Medicine

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Leach, J.P., Martin, J.F. Cardiomyocyte Proliferation for Therapeutic Regeneration. Curr Cardiol Rep 20, 63 (2018). https://doi.org/10.1007/s11886-018-1011-x

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