Development of new cardiovascular regeneration therapy by regulating apoptosis and bone marrow stem cell mobilization

我们已经报道了通过将自体骨髓细胞移植到缺血肢体来治疗血管生成的有效性和安全性；然而，这种治疗需要全身麻醉才能获得骨髓细胞。为了利用骨髓细胞开发更有效的治疗方法，我们检测了G-CSF、M-CSF和促红细胞生成素(EPO)等多种因素对心血管疾病大鼠和小鼠骨髓细胞凋亡和动员的调节作用。本研究的主要发现是：(1)G-CSF动员内皮祖细胞，促进血管损伤后内皮祖细胞的再内皮化，减少新生内膜形成；(2)M-CSF通过激活SDF-1/CXCR4系统在血管损伤后早期诱导新生内膜形成；(3)EPO减少炎症细胞的浸润和细胞因子的表达，改善自身免疫性心肌炎的心功能，减轻心脏炎症。这些发现表明了这些因子在心血管疾病中的治疗潜力。

We have previously reported the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow cells to ischemic limbs ; however, this therapy needs general anesthesia to obtain bone marrow cells. To develop more efficient therapy using bone marrow cells, we examined the effect of several factors, such as G-CSF, M-CSF, and erythropoietin (EPO), that regulate apoptosis and bone marrow cell mobilization in rat and murine models of cardiovascular diseases. The major findings of this study are : (1) G-CSF mobilized endothelial progenitor cells, accelerated reendothelialization, and decreased neointimal formation after vascular injury ; (2) M-CSF induced neointimal formation in the early stages after vascular injury through activation of SDF-1/CXCR4 system ; (3) EPO attenuated inflammatory cell infiltration and cytokine expression, and it improved cardiac function and reduced cardiac inflammation in autoimmune myocarditis. These findings suggest the therapeutic potential of these factors in cardiovascular diseases.