Background: We have previously reported that aging of stem cells compromises their growth and proliferation potential and their regenerative capacity post transplantation in the infarcted heart. We have identified small juvenile population of stem cells in aging rat derived bone marrow (BM) which expressed cardiac lineage markers GATA-4 and MEF-2C. We proposed that these cells possessed great potential for repair of the ischemic heart. Methods and Results: Small cells were isolated from male young ( Yng Small; 8-12 weeks) and old ( Old Small; 24-28 months) Fischer-344 rats BM-stromal cells by filtration through 3 μ m pore sized sieve. The proliferation and colony formation capacity of Yng Small cells and Old Small cells were significantly higher than total population of the old cells ( Old Hetero). Flow cytometry showed both Old Small and Yng Small cells were positive for CD29, CD44, CD59 (Sca-1 homologue) and CD90 but negative for CD45 and CD117 (c-kit). Myocardial regenerative capacity of Old Small and Old Hetero cells was assessed in a rat model of acute myocardial infarction (n=10 /group) using DMEM injected animals as controls. Echocardiography at 4 weeks after cell transplantation showed preserved indices of global heart function including left ventricle (LV) diastolic volume ( Old Hetero: 58.2±3.6 vs Old Small: 40.1±5.4ml, p <0.01), LV ejection fraction ( Old Hetero: 48.2±5.1 vs Old Small: 55.2±3.8%, p <0.05) and fractional shortening ( Old Hetero: 19.8±3.5 vs Old Small: 23.5±2.1%, p <0.05) in Old Small cell treated animals. Histological studies showed smaller infarction size in Old Small cell treated hearts ( Old Hetero: 53.5±3.1 vs Old Small: 41.0±2.9, p <0.01). Border zone capillary density was higher in Old Small group ( Old Hetero: 29.0±9.5 vs Old Small: 39.5±10.2%, p <0.05). We also confirmed that the QDot labeled Old Small cells differentiated into cardiac and endothelial cells as indentified by actinin and vWF-VIII specific immunostaining. Conclusions: Old Small cell transplantation enhanced angiogenesis in border zone of infarcted heart and improved LV function as compared to Old Hetero. These findings suggested that Old Small cells could be excellent source for autologous cell transplantation in elderly patients for better prognosis.