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J Thorac Cardiovasc Surg 2003;126:114-122
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction

^a Division of Cardiothoracic Surgery, Montreal General Hospital, McGill University Health Center, Montreal, Quebec, Canada
^b Department of Cardiovascular Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Read at the Eighty-second Annual Meeting of The American Association for Thoracic Surgery, Washington, DC, May 5-8, 2002.

Received for publication March 29, 2002; revisions received November 19, 2002; accepted for publication December 4, 2002.

^* Address for reprints: Ray C.-J. Chiu, MD, PhD, Division of Cardiothoracic Surgery, The Montreal General Hospital, MUHC, 1650 Cedar Ave, Suite C9-169, Montreal, Quebec H3G 1A4, Canada
rchiu{at}po-box.mcgill.ca

OBJECTIVES: Bone marrow stromal cells are capable of differentiating into cardiomyogenic cells. We tested the hypothesis that transcoronary implantation of bone marrow stromal cells may regenerate infarcted myocardium and reduce cardiac dysfunction.

METHODS: Isolated bone marrow stromal cells from the isogenic donor rats were transfected with LacZ reporter gene for cell labeling. To induce cardiomyogenic differentiation, the bone marrow stromal cells were treated with 5-azacytidine before implantation. Two weeks after left coronary ligation, these cells (1 x 10⁶ in 150 µL) were infused into the briefly distally occluded ascending aorta of the recipient rats (n = 15) to simulate direct coronary infusion clinically. Control animals were infused with cell-free medium (n = 14). Cardiac function was evaluated by echocardiography at preimplantation and 4 and 8 weeks postimplantation. The hearts were then immunohistochemically studied to identify phenotypic changes of implanted bone marrow stromal cells.

RESULTS: Immediately after cell infusion, the bone marrow stromal cells were trapped within coronary vessels in both infarcted and noninfarcted areas. However, after 8 weeks, most of the cells were identified in the scar and periscar tissue, expressing sarcomeric myosin heavy chain and cardiomyocyte-specific protein troponin I-C. Some bone marrow stromal cells were found to be connected to the adjacent host cardiomyocytes with gap junction. Two-way repeated-measures analysis of variance revealed significant improvement in fractional shortening and end-diastolic and end-systolic diameter of the left ventricle (P = .0465, .002, .0004, respectively) in the bone marrow stromal cell group.

CONCLUSIONS: Although bone marrow stromal cells had been reported to improve cardiac function when injected directly into the myocardial scar, this study demonstrated for the first time that bone marrow stromal cells can be delivered via the coronary artery, as they are capable of targeted migration and differentiation into cardiomyocytes in the scar tissue to improve cardiac function.