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(Circulation. 2005;112:I-96 – I-104.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Cell Transplantation Improves Ventricular Function After a Myocardial Infarction

A Preclinical Study of Human Unrestricted Somatic Stem Cells in a Porcine Model

Byung-Ok Kim, MD^*; Hai Tian, MD, PhD^*; Kriengchai Prasongsukarn, MD; Jun Wu, MD; Denis Angoulvant, MD; Stephan Wnendt, PhD; Andreas Muhs, PhD; Dimitry Spitkovsky, PhD; Ren-Ke Li, MD, PhD

From the Department of Surgery (B.-O.K., H.T., K.P., J.W., D.A., R.-K.L), Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, Canada; and Kourion Therapeutics AG (S.W., A.M., D.S.), Germany, a subsidiary of ViaCell Inc, Cambridge, Mass.

Correspondence to Ren-Ke Li, MD, PhD, Toronto General Hospital, NU 1-115, 200 Elizabeth St, Toronto, Ontario M5G 2C4, Canada. E-mail renkeli{at}uhnres.utoronto.ca

Background— Cell transplantation offers the promise in the restoration of ventricular function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSCs) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. The present study evaluated the effect of USSCs on myocardial regeneration and improvement of heart function after myocardial infarction in a porcine model.

Method and Results— The distal left anterior descending artery of Yorkshire pigs (30 to 35 kg) was occluded by endovascular implantation of a coil. Four weeks after infarction, single-photon emission computed tomography technetium 99m sestamibi scans (MIBI) and echocardiography were performed. USSCs (100x10⁶) or culture media were then directly injected into the infarcted region (n=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. At 4 weeks after transplantation, MIBI and echocardiography were repeated and heart function was also assessed with a pressure-volume catheter. The infarcted myocardium and implanted cells were studied histologically. MIBI showed improved regional perfusion (P<0.05) and wall motion (P<0.05) of the infarct region in the transplant group compared with the control. Ejection fraction evaluated by both MIBI and echocardiography decreased in the control group but increased in the transplant group (P<0.01). Scar thickness of the transplant group was higher than the control. The grafted cells were detected 4 weeks after transplantation by both immunohistochemistry and in situ hybridization.

Conclusion— Engrafted USSCs were detected in the infarct region 4 weeks after cell transplantation, and the implanted cells improved regional and global function of the porcine heart after a myocardial infarction. This study suggests that the USSC implantation will be efficacious for cellular cardiomyoplasty.

Key Words: myocardial infarction • heart failure • cells • transplantation