considered unusual cells that are created only during embryonic and fetal development so that their total number in the heart is established at birth and no further growth occurs postnatally, in adulthood, or during senescence. 2, 24 This paradigm refutes the belief that all cardiomyocytes have the same age and that the age of these cells corresponds to the age of the organ and organism. Similarly, this paradigm suggests that the turnover and growth of vascular SMCs and ECs may be regulated by differentiation of CSCs more than by the ability of these mature cells to reenter the cell cycle and divide.

Thus, a new conceptual framework of the heart has emerged. The heart is now viewed as a self-renewing organ in which myocyte regeneration occurs throughout the organism lifespan (Figure 1). Myocytes are the progeny of resident CSCs stored in niches. The niches control the turnover of