Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse
Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse
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DOI：
10.1161/hh0302.104460
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发表时间：
2002-02-22
影响因子：
20.1
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Zhang, ZG;Zhang, L;Chopp, M
我们研究了循环内皮祖细胞是否有助于中风后的新血管形成。将从组成型表达由内皮特异性启动子Tie 2转录调控的β-半乳糖苷酶的转基因小鼠获得的供体骨髓细胞注射到成年小鼠中。栓塞大脑中动脉（MCA）造成局灶性脑缺血，采用灌注加权磁共振成像（MRI）检测脑血流量（CBF）的变化。采用激光扫描共聚焦显微镜（LSCM）、免疫组化和X-gal染色。灌注加权MRI显示缺血后1个月，梗死区边界周围的CBF增加。形态学和三维图像分析显示，扩大和薄壁血管发芽或肠套叠在缺血性病变的边界，这密切对应于灌注加权MRI检测到的CBF区域升高，表明存在新血管形成。X-gal和双重免疫染色表明，Tie 2-lacZ阳性细胞纳入网站的新生血管在梗死的边界，这些细胞表现出内皮抗原标记物（血管性血友病因子）。此外，没有缺血的骨髓受体小鼠显示Tie 2-lacZ表达细胞掺入脉络丛血管中。这些数据表明，中风后成人脑中新血管的形成不仅限于血管生成，而且还涉及血管发生，并且来自骨髓的循环内皮祖细胞有助于脉络丛的血管亚结构。
We investigated whether circulating endothelial progenitor cells contribute to neovascularization after stroke. Donor bone marrow cells obtained from transgenic mice constitutively expressing beta-galactosidase transcriptionally regulated by an endothelial-specific promoter, Tie2, were injected into adult mice. Focal cerebral ischemia was induced by embolic middle cerebral artery (MCA) occlusion and changes of cerebral blood flow (CBF) were measured by perfusion-weighted magnetic resonance imaging (MRI). Laser scanning confocal microscopy (LSCM), immunohistochemistry and X-gal staining were performed. Perfusion-weighted MRI demonstrated increases in CBF around the boundary of an infarct area I month after ischemia. Morphological and 3-dimensional image analyses revealed enlarged and thin-walled blood vessels with sprouting or intussusception at the boundary of the ischemic lesion, which closely corresponded to elevated CBF areas detected on perfusion-weighted MRI, indicating the presence of neovascularization. X-gal and double immunostaining demonstrated that Tie2-lacZ-positive cells incorporated into sites of neovascularization at the border of the infarct, and these cells exhibited an endothelial antigenic marker (von Willebrand factor). In addition, bone marrow recipient mice without ischemia showed incorporation of Tie2-lacZ- expressing cells into vessels of the choroid plexus. These data suggest that formation of new blood vessels in the adult brain after stroke is not restricted to angiogenesis but also involves vasculogenesis and that circulating endothelial progenitor cells from bone marrow contribute to the vascular substructure of the choroid plexus.