Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia
Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia
复制标题
Netrin-1促进肢体缺血的间充质干细胞血运重建
DOI：
10.1177/1479164115611594
复制
发表时间：
2016-03-01
影响因子：
2.4
通讯作者：
Li, Qian
中科院分区：
文献类型：
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作者：
Ke, Xianjin;Liu, Chenxiao;Li, Qian
本研究探讨Netrin-1对骨髓间充质干细胞血管生成的影响及其作用机制。细胞培养中观察骨髓间充质干细胞的管状形成和迁移。在手术后第一天将骨髓间充质干细胞或Netrin-1-骨髓间充质干细胞注射到大鼠后肢的缺血区域。采用激光多普勒血流灌注成像技术检测血浆和肌肉中血管内皮生长因子的水平，免疫组织化学和免疫荧光技术检测血管生成。与未处理对照组相比，含有Netrin-1的培养基中的骨髓间充质干细胞显着增加了骨髓间充质干细胞的管形成和迁移的数量。Netrin-1在肾小管形成和迁移中的作用与血管内皮生长因子相似，与血管内皮生长因子联合应用时，Netrin-1的作用比其他3组更强。Netrin-1-骨髓间充质干细胞组比注射骨髓间充质干细胞组（单独使用骨髓间充质干细胞治疗）或对照组（使用培养基治疗）具有更好的增加血液灌注评分和血管密度，以及改善缺血肢体的功能。这些结果表明，Netrin-1具有增强骨髓间充质干细胞血管生成的能力，并通过增加血管内皮生长因子的水平来改善缺血后肢的功能。
This study examines the effect and mechanism of action of Netrin-1 on bone marrow mesenchymal stem cells in angiogenesis. Tube formation and migration of bone marrow mesenchymal stem cells were observed in cell culture. Bone marrow mesenchymal stem cells or Netrin-1-bone marrow mesenchymal stem cells were injected into the ischaemic area of the rat hind limb on the first day after surgery. Laser Doppler perfusion imaging was performed to analyse the levels of vascular endothelial growth factor in plasma and muscles, and immunohistochemistry and immunofluorescence were used to analyse angiogenesis. Bone marrow mesenchymal stem cells in medium containing Netrin-1 markedly increased the number of tubes formed and the migration of bone marrow mesenchymal stem cells compared with the untreated control group. The function of Netrin-1 in tube formation and migration is similar to vascular endothelial growth factor, and combined with vascular endothelial growth factor, Netrin-1 has more enhanced effect than in the other three groups. The Netrin-1-bone marrow mesenchymal stem cell group had better augmented blood-perfusion scores and vessel densities, as well as improved function of the ischaemic limb than that of the group injected with bone marrow mesenchymal stem cells (treated with bone marrow mesenchymal stem cells individually) or the control group (treated with medium). These results suggest that Netrin-1 has the ability to augment the angiogenesis of bone marrow mesenchymal stem cells and improve the function of the ischaemic hind limb by increasing the level of vascular endothelial growth factor.