Mechanism-Based Cardiac Regeneration Strategies in Mammals

• Type of Material: Article
• Authors: Nawazish Naqvi, Emory University; Siiri E Iismaa, Victor Chang Cardiac Research Institute; Robert M Graham, Victor Chang Cardiac Research Institute; Ahsan Husain, Emory University
• Language: English
• Date: 2021-10-11
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Naqvi, Iismaa, Graham and Husain.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fcell.2021.747842
• Title of Journal or Parent Work: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
• Volume: 9
• Start Page: 747842
• End Page: 747842
• Grant/Funding Information: This work was supported by grants from the Department of Medicine, Emory University, the NIH (HL127726 and T32 HL007745), The American Heart Association (13SDG16460006 and 17GRNT33670975), the Fondation Leducq Transatlantic Network, National Health and Medical Research Council, Australia (APP1074386), R.T. Hall estate, and the Australian Research Council Stem Cells Australia Special Initiative in Stem Cell Science grant (SR1101002).
• Keywords: cardioprotection; cardiomyocyte proliferation; GROWTH; PROLIFERATION; STEM-CELLS; HEART REGENERATION; Science & Technology; REPAIR; ischemic injury; Life Sciences & Biomedicine; Developmental Biology; cardiac regeneration; REPERFUSION; MYOCARDIAL-INFARCTION; SURVIVAL; heart failure; Cell Biology; CARDIOMYOCYTE DNA-SYNTHESIS; QUALITY-OF-LIFE
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Heart failure in adults is a leading cause of morbidity and mortality worldwide. It can arise from a variety of diseases, with most resulting in a loss of cardiomyocytes that cannot be replaced due to their inability to replicate, as well as to a lack of resident cardiomyocyte progenitor cells in the adult heart. Identifying and exploiting mechanisms underlying loss of developmental cardiomyocyte replicative capacity has proved to be useful in developing therapeutics to effect adult cardiac regeneration. Of course, effective regeneration of myocardium after injury requires not just expansion of cardiomyocytes, but also neovascularization to allow appropriate perfusion and resolution of injury-induced inflammation and interstitial fibrosis, but also reversal of adverse left ventricular remodeling. In addition to overcoming these challenges, a regenerative therapy needs to be safe and easily translatable. Failure to address these critical issues will delay the translation of regenerative approaches. This review critically analyzes current regenerative approaches while also providing a framework for future experimental studies aimed at enhancing success in regenerating the injured heart.