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

被引:24
作者
Chen, Guangyong
Nayan, Madhur
Duong, Minh
Asenjo, Juan-Francisco
Ge, Yin
Chiu, Ray C-J
Shum-Tim, Dominique
机构
[1] McGill Univ, Div Cardiac Surg, Ctr Hlth, Montreal, PQ H3G 1A4, Canada
[2] McGill Univ, Div Surg Res, Ctr Hlth, Montreal, PQ H3G 1A4, Canada
[3] McGill Univ, Dept Anesthesia, Ctr Hlth, Montreal, PQ H3G 1A4, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
MESENCHYMAL STEM-CELLS; MYOCARDIAL REGENERATIVE THERAPY; INTRAMYOCARDIAL INJECTION; EXTRACELLULAR-MATRIX; TRANSPLANTATION; INFARCTION; DIFFERENTIATION; EXPRESSION; METALLOPROTEINASE; CARDIOMYOCYTES;
D O I
10.1016/j.athoracsur.2010.02.074
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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)-1 beta, 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.
引用
收藏
页码:190 / 198
页数:10
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