Improved Heart Function with Myogenesis and Angiogenesis After Stromal Cell Transplantation
Objective:
The study evaluated the utility of transplanting bone marrow stromal cells in a porcine myocardial infarction model.
Methods:
A myocardial infarction was created by occluding the distal left anterior descending artery in pigs with coils and Gelfoam sponge. Sternal bone marrow was aspirated, and stromal cells were cultured and induced to differentiate to a myogenic phenotype with 5-azacytidine. Four weeks after coronary artery occlusion, sestamibi technetium single-photon emission computed tomographic scans were performed, and then either a graft of 100 x 106 bone marrow stromal cells (n = 5, 30% labeled with bromodeoxyuridine) or culture medium (n = 6) was injected into the infarct region. Four weeks later the tomographic scans were repeated and cardiac function was assessed with pressure and volume measurements. Morphologic and histologic characteristics of the heart were also studied.
Results:
Histologic examination found bromodeoxyuridine-labeled cells within the infarct region in islands that had sarcomeres and Z-bands and stained positively for cardiac specific troponin I. The bone marrow stromal cell transplant sites had a greater (P < .05) capillary density than did the control sites. The tomographic scans showed that the hearts with the cell transplants had increases in stroke volume, regional perfusion, and wall motion (P < .05 for all groups) relative to the control hearts. The pressure-volume analysis showed improvement (P < .05) in end-systolic elastance and preload recruitable stroke work in the transplantation group relative to the control group. The left ventricular chamber size was smaller (P < .05) and the scar thickness was greater (P < .05) in the hearts with transplanted cells than in the control hearts (P = .06).
Conclusion:
5-Azacytidine-treated bone marrow stromal cells transplanted into the myocardial infarct region formed islands of cardiac-like tissue, induced angiogenesis, prevented thinning and dilatation of the infarct region, and improved regional and global contractile function.
From the Toronto General Research Institute, Division of Cardiovascular Surgery, and Division of Clinical Biochemistry, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Supported by research grants to R.K.L. from the Medical Research Council of Canada (MT-13665). R.K.L. is a Career Investigator of the Heart and Stroke Foundation of Ontario.
Received for publication July 11, 2001. Revisions requested Aug 3, 2001; revisions received Aug 31, 2001. Accepted for publication Sept 18, 2001.
Address for reprints: Ren-Ke Li, MD, Toronto General Hospital, CCRW 1-815, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4 (E-mail: [email protected]).
