Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin
Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin
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DOI：
10.1016/j.mvr.2012.02.011
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发表时间：
2012-05-01
影响因子：
3.1
通讯作者：
Plock, Jan A.
中科院分区：
文献类型：
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作者：
Schlosser, Stefan;Dennler, Cyrill;Plock, Jan A.
关于缺血性血管再生的新理论已经出现，表明成体干细胞的关键作用。本研究的目的是研究循环骨髓间充质干细胞（MSCs）在严重缺血小鼠皮瓣模型中的归巢和血流动力学效应。骨髓来源的间充质干细胞(Lin（-)CD105(+)）来自GFP（+）供体小鼠，并转移到野生型C57BL/6小鼠。接受GFP(+)-成纤维细胞治疗的动物作为对照组。两周内采用激光扫描共聚焦显微镜和活体荧光显微镜对干细胞归一和微血流动力学进行形态学分析、监测和定量评估。免疫组化染色GFP、eNOS、iNOS、VEGF。tunel法检测组织活力。我们能够可视化MSCs在体内的血管周围归巢。4天后，MSCs沿血管壁排列，观察期间未发生内皮细胞或平滑肌细胞分化。对照组逐渐增加的动脉血管阻力在给药MSC后消失(P
New theories on the regeneration of ischemic vasculature have emerged indicating a pivotal role of adult stem cells. The aim of this study was to investigate homing and hemodynamic effects of circulating bone marrow-derived mesenchymal stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow-derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)-fibroblasts served as a control group. Laser scanning confocal microscopy and intravital fluorescence microscopy were used for morphological analysis, monitoring and quantitative assessment of the stem cell homing and microhemodynamics over two weeks. Immunohistochemical staining was performed for GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay.We were able to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned along the vascular wall without undergoing endothelial or smooth muscle cell differentiation during the observation period. The gradual increase in arterial vascular resistance observed in the control group was abolished after MSC administration (P