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Original Articles: Adult Cardiac

Marrow Stromal Cells for Cell-Based Therapy: The Role of Antiinflammatory Cytokines in Cellular Cardiomyoplasty

^a Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, Montreal, Quebec, Canada
^b Department of Anesthesia, McGill University Health Center, Montreal, Quebec, Canada

Accepted for publication February 26, 2010.

^_* Address correspondence to Dr Shum-Tim, Division of Cardiothoracic Surgery, McGill University Health Center, 1650 Cedar Ave, Ste C9-169, Montreal, QC H3G 1A4, Canada (Email: dshumtim{at}yahoo.ca).

Background: The mechanism by which marrow stromal cells (MSCs) improve cardiac function after myocardial infarction (MI) is still unclear. Because MI patients with lower circulating proinflammatory/antiinflammatory cytokine ratios have been reported to have a better prognosis and in vitro studies showed that MSCs express antiinflammatory cytokines, we hypothesized that changes in cytokine ratios in the infarct microenvironment after MSC therapy may play a role in improving early cardiac function after MI.

Methods: Sixty-three rats that survived left coronary artery ligations were injected with culture media (group M) or MSCs (group C). Cardiac functional changes were assessed with echocardiography. Cytokine gene expressions of interleukin (IL)-1β, IL-6, IL-8, (proinflammatory) and IL-10 (antiinflammatory) were quantified by real-time polymerase chain reaction. Extracellular matrix deposition, injury score, and the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 ratio were also analyzed.

Results: The ratio of proinflammatory/antiinflammatory cytokine gene expression was decreased in group C at various times, particularly in the early postoperative period. In group C, the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 gene expression ratio was significantly lower than group M at the early phase (12 hours), which in group C was translated into significantly lower extracellular matrix deposition at 24 hours, 1, and 2 weeks. Functional recovery was also significantly better in cell therapy group C.

Conclusions: Our data demonstrate that MSC therapy decreases the proinflammatory/antiinflammatory cytokine ratio in the microenvironment early after MI. This is associated with subsequent less scar formation and improved cardiac function.

Related Article

Invited Commentary

Sunjay Kaushal and Loren E. Wold
Ann. Thorac. Surg. 2010 90: 197-198. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				M. Nayan, A. Paul, G. Chen, R. C. J. Chiu, S. Prakash, and D. Shum-Tim Superior Therapeutic Potential of Young Bone Marrow Mesenchymal Stem Cells by Direct Intramyocardial Delivery in Aged Recipients with Acute Myocardial Infarction: In Vitro and In Vivo Investigation Journal of Tissue Engineering, October 6, 2011; (2011) 741213v1. [Abstract] [Full Text] [PDF]

				S. Kaushal and L. E. Wold Invited Commentary Ann. Thorac. Surg., July 1, 2010; 90(1): 197 - 198. [Full Text] [PDF]