Scar formation following an ischemic insult to the heart is referred to as reparative fibrosis and represents an essential physiological response to heal the damaged myocardium. The biological events of reparative fibrosis include inflammation, the deposition of collagen by myofibroblasts, sympathetic innervation, and angiogenesis. Several studies have further reported that scar formation was associated with the recruitment of neural crest-derived cardiac resident nestin(+) cells that display characteristics consistent with a neural progenitor/stem cell phenotype. During the reparative fibrotic response, these nestin(+) cells participate in neural remodeling and represent a novel cellular substrate of angiogenesis. In addition, a subpopulation of nestin(+) cells identified in the normal heart expressed cardiac progenitor transcriptional factors and may directly contribute to myocardial regeneration following ischemic damage. Nestin protein was also detected in endothelial cells of newly formed blood vessels in the scar and may represent a marker of revascularization. Lastly, nestin was induced in a subpopulation of smooth muscle α-actin(+) scar-derived myofibroblasts, and the expression of the intermediate filament protein may provide a proliferative advantage. Collectively, these data demonstrate that diverse populations of nestin(+) cells participate in cardiac wound healing.