Mammalian heart renewal by pre-existing cardiomyocytes

Hydrogen peroxide primes heart regeneration with a derepression mechanism

“…The dedifferentiation model for the cellular sources of cardiac repair/regeneration was supported by the fact that cardiac muscles mainly regenerate from pre-existing cardiomyocytes after injury in zebrafish [8,9] and mammals [10][11][12]. The stem cell/progenitor cell model for cardiac regeneration in mammals was also recognized by the existence of Sca1 + and c-Kit + cardiac stem cells in mice [13,14], while the transdifferentiation or lineage reprogramming model was proposed partly based on the ability of cardiac fibroblast transdifferentiation into myocytes upon induction by reprogramming factors or microRNA in mice [15][16][17] and reprogramming of embryonic atrial into ventricular myocytes after injury in zebrafish [18].…”

Concise Review: Mechanotransduction via p190RhoGAP Regulates a Switch Between Cardiomyogenic and Endothelial Lineages in Adult Cardiac Progenitors

“…Additionally cardiac tissue contains other cell types, including fibroblasts and smooth muscle cells. Although the intrinsic capacity of heart to regenerate is limited, recent studies suggested a measureable turnover of cardiomyocytes, with yearly rates varying from 1% to 4%-10% or even higher [2,[15][16][17]. Emerging evidence suggests that the cardiac tissue does contain endogenous pool of multipotent stem cells, which are capable of differentiating into cardiomyocytes, endothelial cells, and smooth muscle cells, and that these progenitors are essential for cardiac repair and regeneration [18][19][20][21][22][23][24][25][26].…”

Engineering Cardiovascular Regeneration

“…This view was challenged by describing substantial rates of cardiomyocyte cell division and turnover [2] and with reports of the influx of bone marrow-derived cells with potential for cardiac transdifferentiation [3]. Today, 15 years later, though still controversial, most researchers would agree that (i) the turnover rate of the adult human (as well as murine) heart is less than 1 % per year, i.e., that we die with a relevant fraction of cardiomyocytes as old as ourselves [4], (ii) the few new myocytes that develop during adulthood derive from resident cardiomyocytes by cell division rather than from a Bresident cardiac stem cell^source [5] or bone marrow-derived cells, and (iii) the regeneration is too low to be clinically meaningful, i.e., current levels of regeneration are not able to rescue heart function after a large MI. Thus, patients experiencing a significant loss of muscle mass (>1/3 of the left ventricle) develop heart failure and have a poor prognosis [6].…”