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Mechanisms of myocardial repair by cell-based therapy

细胞疗法的心肌修复机制

基本信息

批准号：
18591550
负责人：
MORIKAGE Noriyasu
金额：
$ 2.38万
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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591550/
关键词：
Bone marrow cells Cardiomyocytes Cytokines

项目摘要

While it is well known that the implantation of bone marrow cells (BMCs) into ischemic hearts can induce angiogenesis and improve cardiac function after myocardial infarction, the precise mechanisms remain unclear. We tested the hypothesis that cytokines produced by BMCs play a key role in this cell-based therapy.BMCs from adult male Wistar rats were cultured under normoxic (20% O2) or hypoxic (1% O2) conditions for 24 hours. ELISA and Western blotting analysis showed that various cytokines, including vascular endothelial growth factor, IL-1β, platelet-derived growth factor, and insulin-like growth factor 1, were produced from BMCs, and that some were enhanced significantly by hypoxia stimulation. Compared with a control blank medium, the supernatant of BMCs cultured under normoxic or hypoxic conditions significantly inhibited apoptosis (p<0.05), and increased the contractive function of isolated adult rat cardiomyocytes in vitro (p<0.05). Using a rat model of acute myocardial infarction, we injected the supernatant of BMCs or control medium intramyocardially on day 0, and then intraperitoneally on days 2, 4, and 6 after infarction. Compared with the control medium, administering the supernatant of BMCs cultured under both normoxic or hypoxic significantly increased the microvessel density and decreased the fibrotic area in the infarcted myocardium, which contributed to a significant improvement in cardiac function at days 7 after infarction (p<0.05).These results show that various cytokines were produced from BMCs, and these cytokines contributed to functional improvement of the infarcted heart, by directly protecting cardiomyocytes against ischemic injury, inducing therapeutic angiogenesis, and inhibiting remodeling of the infarcted heart.

虽然众所周知，将骨髓细胞（BMC）植入缺血心脏可以诱导血管生成并改善心肌梗死后的心脏功能，但其确切机制仍不清楚。我们测试了 BMC 产生的细胞因子在这种基于细胞的疗法中发挥关键作用的假设。来自成年雄性 Wistar 大鼠的 BMC 在常氧 (20% O2) 或低氧 (1% O2) 条件下培养 24 小时。 ELISA和Western blotting分析显示，BMCs产生多种细胞因子，包括血管内皮生长因子、IL-1β、血小板源性生长因子和胰岛素样生长因子1，并且某些细胞因子在缺氧刺激下显着增强。与对照空白培养基相比，常氧或低氧条件下培养的BMC上清液显着抑制细胞凋亡（p<0.05），并增强离体成年大鼠心肌细胞的体外收缩功能（p<0.05）。使用急性心肌梗塞大鼠模型，我们在第0天将BMC上清液或对照培养基注射到心肌内，然后在梗塞后第2、4和6天腹腔内注射。与对照培养基相比，给予常氧或低氧条件下培养的BMC上清液显着增加了梗死心肌中的微血管密度并减少了纤维化面积，这有助于梗塞后7天的心功能显着改善（p<0.05）。这些结果表明BMC产生了多种细胞因子，这些细胞因子有助于功能改善通过直接保护心肌细胞免受缺血性损伤、诱导治疗性血管生成和抑制梗塞心脏的重塑，从而对梗塞心脏产生保护作用。