Improvement of endothelial function by systemic transfusion of vascular progenitor cells
Improvement of endothelial function by systemic transfusion of vascular progenitor cells
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DOI：
10.1161/01.res.0000246095.90247.d4
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发表时间：
2006-10-13
影响因子：
20.1
通讯作者：
Nickenig, Georg
中科院分区：
文献类型：
--
作者：
Wassmann, Sven;Werner, Nikos;Nickenig, Georg
内皮功能障碍以血管反应性异常为特征，是动脉粥样硬化程度的标志。循环祖细胞对持续血管损伤的细胞修复对血管的完整性和功能可能是必不可少的，并可能限制血管反应性的异常。将载脂蛋白E基因缺陷(apoE(-/-))小鼠切除脾，给予高脂饮食5周后，与野生型小鼠比较，主动脉段内皮依赖性血管扩张功能明显受损。从野生型小鼠分离的2×10(7)个脾单个核细胞(MNC)连续3天静脉输注后，apoE(-/-)小鼠的内皮依赖性血管扩张功能在输注后7、14和45天得到恢复。对主动脉组织的组织学分析发现，在动脉粥样硬化病变的内皮细胞层中，荧光标记的外源性祖细胞表达内皮细胞标记CD31。祖细胞处理导致血管一氧化氮合酶活性增加。输注体外分化的Dil-ac-LDL/凝集素阳性内皮祖细胞、CD11b阳性(单核细胞标记物)、CD45R阳性(B细胞标记物)或SCA-1阳性(干细胞标记物)MNC亚群均可显著改善内皮依赖性血管扩张，尽管这些治疗不如输注全MNCs有效。与未耗竭的MNCs相比，CD11b阳性、CD45R阳性或SCA-1阳性细胞的MNCs的耗竭导致内皮依赖的血管扩张功能显著减弱，但与生理盐水处理的apoE(-/-)小鼠相比，血管反应性仍显著改善。静脉输注脾来源的单核细胞可改善动脉粥样硬化性载脂蛋白E(-/-)小鼠的内皮依赖性血管扩张，表明循环祖细胞在修复持续的血管损伤中发挥重要作用。超过1个亚群的MNC片段似乎参与了这一效应。
Endothelial dysfunction is characterized by abnormalities in vasoreactivity and is a marker of the extent of atherosclerosis. Cellular repair by circulating progenitor cells of ongoing vascular injury may be essential for vascular integrity and function and may limit abnormalities in vasoreactivity. Apolipoprotein E-deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol diet for 5 weeks, resulting in marked impairment of endothelium-dependent vasodilation of aortic segments as compared with wild-type mice. Intravenous transfusion of 2 X 10(7) spleen-derived mononuclear cells (MNCs) isolated from wild-type mice on 3 consecutive days restored endothelium-dependent vasodilation in the apoE(-/-) mice, as measured 7, 14, and 45 days after transfusion. Histological analyses of aortic tissue identified fluorescent-labeled, exogenously applied progenitor cells that expressed the endothelial cell marker CD31 in the endothelial cell layer of atherosclerotic lesions. Progenitor cell treatment led to increased vascular nitric oxide synthase activity. Transfusion of either in vitro-differentiated Dil-Ac-LDL/lectin-positive endothelial progenitor cells, CD11b-positive (monocyte marker), CD45R-positive (B-cell marker), or Sca-1-positive (stem cell marker) MNC subpopulations significantly improved endothelium-dependent vasodilation, although these treatments were not as effective as transfusion of total MNCs. Depletion of MNCs of either CD11b-positive, CD45R-positive, or Sca-1-positive cells resulted in significant attenuation of endothelium-dependent vasodilation as compared with nondepleted MNCs; however, vasoreactivity was still significantly improved as compared with saline-treated apoE(-/-) mice. Intravenous transfusion of spleen-derived MNCs improves endothelium-dependent vasodilation in atherosclerotic apoE(-/-) mice, indicating an important role of circulating progenitor cells for the repair of ongoing vascular injury. More than 1 subpopulation of the MNC fraction seems to be involved in this effect.