Nearly one million Americans suffer a myocardial infarction each year, many of whom progress to heart failure, the single most common hospital discharge diagnosis in those over age 65 (ref. 1). The adult human heart has a limited regenerative response to injury such that the loss or dysfunction of cardiomyocytes results in reduced pump function, often culminating in heart failure, life-threatening arrhythmias and sudden death. Numerous clinical trials over the past decade have introduced a variety of autologous stem and progenitor cell types into failing human hearts as a strategy for regenerating new myocardium, but exogenous stem cells seem to give rise to few if any new muscle cells, bringing into question the biological basis for the limited functional improvement. Thus, there is still