Bone marrow remains the most frequently used source of adult stem cells, but its angiogenic and possibly also myogenic potentials are likely to regress with increasing donor age and morbidity. Recently, cord blood has been suggested as a readily available source for non-embryonic stem cells with high regenerative capacity. We first tested the capacity of mononuclear cells obtained from human umbilical cord blood (UCB(mn)) to migrate to the heart on IV delivery in NOD/Scid mice. As evidenced by the presence of human DNA by PCR analysis, UCB(mn) cells migrated to the heart in 50% of the mice with myocardial infarctions, but in none of the sham-operated control mice. In UCB(mn) cell-positive injured hearts, the infarct size was smaller and capillary density higher in the ischemic myocardium. By immunohistology, we observed endothelial cell differentiation of UCB(mn) cells in the heart but there was no colocalization of UCB cell-specific antibodies with markers of myocyte-type cells. In a second series of experiments, we injected 5 x 10(5) UCB cells enriched for CD133 directly into the necrotic myocardium of NOD/Scid mice. Comparisons were performed with an equivalent number of CD133+ bone marrow (BM) cells or a sham injection in the respective control groups. Both BMCD133+ and UCBCD133+ cells abolished postoperative mortality and improved capillary density in the injured myocardium, but only BMCD133+ cells led to a detectable improvement in myocardial contractility in vivo. We conclude that human UCB cells facilitated neovascularization of ischemic myocardium, but their capacity for formation of contractile neotissue needs further investigation.