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Eur J Cardiothorac Surg 2003;24:393-398
© 2003 Elsevier Science NL


Mobilization and homing of bone marrow stromal cells in myocardial infarction

Bindu Bittira, Dominique Shum-Tim, Abdulaziz Al-Khaldi, Ray C-J. Chiu*

Division of Cardiothoracic Surgery, McGill University Health Center, Montreal, Quebec, Canada

Received 25 September 2002; received in revised form 17 April 2003; accepted 26 April 2003.

* Corresponding author. The Montreal General Hospital, McGill University Health Center C9-169, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4. Tel.: +1-514-934-1934x42839; fax: +1-514-934-8289
e-mail: ray.chiu{at}mcgill.ca

Objective: Marrow stromal cells (MSCs) contain multipotent cells, which may participate in the repair of damaged organs. We tested the hypothesis that MSCs are recruited to the heart upon myocardial infarction (MI), and play pathophysiological roles in the healing and adaptation process. Methods: Donor MSCs from isogenic Lewis rats were harvested, multiplied and labeled with Lac Z reporter gene. Ten million labeled cells were injected intravenously into the recipient rats (n=30). One week later, 10 rats were killed to examine the distribution of the labeled MSCs. Other rats underwent either coronary artery ligations (n=14) or sham operations (n=6). The hearts were removed at various time points (1–8 weeks) and stained for ß-galactosidase activity. Phenotypes of labeled cells were identified with immunohistochemical stains. Results: In rats killed at 1 week, labeled cells had homed into the bone marrow of the recipients, and none found in their hearts. In the coronary ligated hearts, labeled cells were seen in and near the infarct at all time points studied (14/14), but none in the sham operated hearts (6/6). There was evidence for myogenic differentiation. Some of these labeled cells showed positive staining for cardiomyocyte specific troponin I-c at 4 weeks, while others appeared in the vascular walls expressing smooth muscle alpha-actin. Conclusions: Following myocardial infarction, MSC's are signaled and recruited to the injured heart, where they undergo differentiation, and may participate in the pathophysiology of post-infarct remodeling, angiogenesis, and maturation of the scar. Therapeutic implantation of MSCs thus may further enhance such effects.

Key Words: Myocardial infarction • Adult stem cells • Physiology • Myocytes • Angiogenesis




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