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Mechanisms of bone marrow stem cells for myocardial repair

骨髓干细胞修复心肌的机制

基本信息

批准号：
17591472
负责人：
MIKAMO Akihito
金额：
$ 2.18万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591472/
关键词：
Bone marrow stem cell Therapeutic angiogenesis Regenerative medicine

项目摘要

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.

尽管细胞疗法作为一种治疗心力衰竭的新策略显示出巨大的前景，但其确切的机制仍不清楚。此外，细胞治疗相对于传统细胞因子治疗的优势还有待阐明。本研究旨在比较细胞治疗和细胞因子治疗在缺血性和非缺血性心力衰竭实验模型中所取得的功能改善。结扎小鼠左前降支建立缺血性心力衰竭模型，阿霉素腹腔注射诱导小鼠非缺血性心力衰竭模型。建立心力衰竭模型后，随机给予小鼠心肌内注射2x10^5c-kit阳性的骨髓干细胞(细胞治疗)、肝生长因子(细胞因子治疗)或仅注射PBS(对照)。在缺血性心力衰竭模型中，细胞治疗和细胞因子治疗均显著增加缺血心肌血管密度，抑制心肌细胞凋亡，缩小心肌纤维化面积，使小鼠存活率显著提高，心功能明显增强(与对照组比较P&lt；0.05)。在非缺血性心力衰竭模型中，细胞治疗显著提高存活率和心功能(P&lt；0.05与对照治疗相比)，但细胞因子治疗不能，尽管细胞因子治疗抑制心肌细胞的纤维化和凋亡。细胞疗法和细胞因子疗法都是治疗缺血性心力衰竭的替代疗法。然而，对于非缺血性心力衰竭的治疗，细胞疗法比单一生长因子的细胞因子疗法更有效。