| Co-Investigator(Kenkyū-buntansha) |
HAMANO Kimikazu Yamaguchi University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (60263787)
LI Tao-sheng Yamaguchi University, Graduate School of Medicine, Research Associate, 大学院医学系研究科, 助手 (50379997)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and non-ischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and non-ischemic heart failure was induced by an intraperitoneal injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2x10^5 c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p<0.05 vs control therapy). In the non-ischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p<0.05 vs control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of non-ischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.
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