Cardiac stem cells generate new cardiac myocytes during normal cardiac development and pathological hypertrophy

The heart has historically been regarded as a post-mitotic organ incapable of cellular renewal. Recent studies suggest that the adult heart maintains the capacity to generate new myocytes from cardiac stem cells. This study sought to determine if a cell population capable of differentiating into cardiac myocytes was present in the feline heart, if new myocyte formation was part of normal adolescent growth in the feline myocardium, and if the newly formed myocytes had functionally distinct calcium handling and contractile properties. We further examined if newly formed myocytes contributed to the pathological growth of the heart induced by hemodynamic stress, and if those newly formed myocytes exhibited a dysfunctional phenotype.;We identified a population of immature cells in the healthy adolescent feline heart that expressed the stem cell marker c-kit and differentiated into endothelial cells, smooth muscle cells, and cardiac myocytes in vitro. We found that new myocyte formation contributes significantly to the adolescent growth of the feline heart; that the adolescent heart has a population of small mononucleated ventricular myocytes that show evidence of cell cycle activity and proliferative potential; and that these new myocytes have physiological properties reminiscent of fetal or neonatal myocytes.;In the pressure overloaded heart, we found that the increase in heart size is significantly greater than the increase in myocyte volume; that evidence of cell cycle activity is higher in small, mononucleated myocytes than in large, binucleated myocytes; that the ratio of mono- to binucleated myocytes does not change; and that the small, mononucleated myocytes have contractile properties similar to binucleated myocytes from the stressed hearts. These data support our hypothesis that myocyte hyperplasia contributes significantly to cardiac growth in response to pressure overload.;This endogenous growth and repair mechanism in the young heart offers optimism for therapeutic application in heart failure.