Heart Factory or Fiction? Cardiac Progenitor Cells and Regeneration

> “Create in me a clean heart, O God.” Psalm 51:10 In the Christian tradition, the doctrine of regeneration considers the “deceitful…and wicked” heart a vessel for accepting God and thereby being born again. Indeed, many cultures have invested the heart with powers well beyond its biological role in maintaining systemic perfusion. However, the capacity of the heart for renewal was limited to metaphor until relatively recently, when science revealed a very literal interpretation of cardiac regeneration. Contrary to long-standing belief, it now appears that new cardiomyocytes are created after birth and that cardiomyocyte renewal continues in the aging human heart. Most studies estimate that the annual rate of myocyte renewal is roughly 1%,1,2 although other groups suggest that up to 40% of a heart’s cardiomyocytes might be regenerated each year.3 These new cells may arise from resident cardiac progenitor cells (CPCs), from proliferation of preexisting cardiomyocytes, or from migratory populations of epicardial cells. Regardless of their origin, their number and inherent function seem insufficient to heal the profoundly injured heart because roughly 300 000 Americans die every year of heart failure. Of course, the more sanguine among us view this striking burden of disease as a therapeutic opportunity, and clinical trials of myocardial regeneration using various cell types and preparations already have been conducted. Early trials in the field used bone marrow–derived stem cells with mixed results.4 More recently, 2 trials have investigated the use …