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Stem Cells International
Volume 2016, Article ID 6193419, 17 pages
Review Article

Repair Injured Heart by Regulating Cardiac Regenerative Signals

1Department of Pathology & Lab Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
2Department of Pharmacology & Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
3Infectious Disease Hospital, Nanchang University, Nanchang, Jiangxi 330002, China

Received 16 March 2016; Revised 27 June 2016; Accepted 29 June 2016

Academic Editor: Benedetta Bussolati

Copyright © 2016 Wen-Feng Cai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cardiac regeneration is a homeostatic cardiogenic process by which the sections of malfunctioning adult cardiovascular tissues are repaired and renewed employing a combination of both cardiomyogenesis and angiogenesis. Unfortunately, while high-quality regeneration can be performed in amphibians and zebrafish hearts, mammalian hearts do not respond in kind. Indeed, a long-term loss of proliferative capacity in mammalian adult cardiomyocytes in combination with dysregulated induction of tissue fibrosis impairs mammalian endogenous heart regenerative capacity, leading to deleterious cardiac remodeling at the end stage of heart failure. Interestingly, several studies have demonstrated that cardiomyocyte proliferation capacity is retained in mammals very soon after birth, and cardiac regeneration potential is correspondingly preserved in some preadolescent vertebrates after myocardial infarction. There is therefore great interest in uncovering the molecular mechanisms that may allow heart regeneration during adult stages. This review will summarize recent findings on cardiac regenerative regulatory mechanisms, especially with respect to extracellular signals and intracellular pathways that may provide novel therapeutics for heart diseases. Particularly, both in vitro and in vivo experimental evidences will be presented to highlight the functional role of these signaling cascades in regulating cardiomyocyte proliferation, cardiomyocyte growth, and maturation, with special emphasis on their responses to heart tissue injury.