BACKGROUND: Cell transplantation offers the promise to restore function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSC) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. Present study evaluated USSCs on myocardial regeneration and improvement of heart function in a porcine model. Method: The distal LAD artery of Yorkshire pigs (30kg) was occluded with a coil. Four weeks after infarction SPECT MIBI scan (MIBI) and echocardiography (Echo) were performed and USSCs (100 x 106) or culture media were then directly injected into the infarcted region (N=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. MIBI and Echo were repeated 4 weeks after transplantation and the function was also assessed with pressure volume catheter. Infarcted myocardium and implanted cells were studied histologically. Results: Four weeks after transplantation, MIBI showed improved regional perfusion (p<0.05) and wall motion (p<0.05) of the infarcted region in the transplanted group compared to the controls. Ejection fraction evaluated by both MIBI and Echo decreased in the control group but increased in the transplant group (p<0.01). Preload recruitable stroke work was greater (p<0.05) in the transplanted hearts than control hearts. Scar area and thickness of USSC group was higher than controls. In transplant group neither angioma nor teratoma was observed. Transplanted cells were detected 4 weeks after transplantation with the help of a human specific antibody. Conclusion: USSC transplantation improved regional and global function of porcine heart after myocardial infarction. Engrafted USSCs can be detected in transplanted tissue at 4 weeks post transplantation. The study suggested the efficacy and safety of USSCs for cellular cardiomyoplasty.