Marrow stromal cells for cell-based therapy: the role of antiinflammatory cytokines in cellular cardiomyoplasty.
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)-1beta, 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.
Chen
Guangyong
G
Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, Montreal, Quebec, Canada.
Nayan
Madhur
M
Duong
Minh
M
Asenjo
Juan-Francisco
JF
Ge
Yin
Y
Chiu
Ray C-J
RC
Shum-Tim
Dominique
D
D000818:Animals; D016026:Bone Marrow Transplantation; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D017154:Stromal Cells / Q000276:immunology / Q000637:transplantation*
D016207:Cytokines