Bone marrow (BM)–derived cell therapy for the damaged heart has now been under investigation for almost 2 decades. Right from the outset, both in vitro and in animal models of cardiac damage, early studies using BM-derived cells showed incredible promise and reported numerous broadly positive findings, driving enthusiasm for the clinical translation of this approach. To mention just a few of those early studies, findings from the late 1990s included the successful differentiation of BM stromal cells into cardiomyocyte-like cells1; increased angiogenesis and the formation of cardiomyocyte-like cells in vivo when BM-derived cells were injected into the scarred left ventricular (LV) wall2; and the identification that the BM is a reservoir for circulating endothelial progenitor cells that contribute to new vessel formation in the adult.3 Then, in 2001, it was reported that the intravenous administration of human CD34+ BM-derived cells into immune-deficient rats after acute myocardial infarction (MI) led to the proliferation of pre-existing vasculature and de novo new blood vessel formation in the infarct bed, which contributed to the salvage of viable myocardium and dramatic improvements in LV ejection fraction (LVEF).4 Concurrently, others reported that a specific fraction of BM cells that expressed c-kit, but not hematopoietic markers, could give rise not only to new vessels but also to cardiomyocytes5 and that the mobilization of BM cells using specific factors in the post-MI period leads to the homing of these cells to the MI region, reduced infarct size, and improved survival in an animal model.6 Article, see p 1346 With these and other remarkable preclinical studies appearing in rapid succession, clinician scientists were swift to begin investigating BM-derived cells to ameliorate cardiovascular disease in humans.7 Indeed, still in 2001, what we think to be the first human report of …