Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats

Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats
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DOI:
10.1227/01.neu.0000229058.08706.88
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发表时间:
2006-09-01
期刊:
影响因子:
4.8
通讯作者:
Nozaki, Kazuhiko
Nozaki, Kazuhiko
中科院分区:
医学1区
文献类型:
--
作者:
Ohta, Tsuyoshi;Kikuta, Ken-ichiro;Nozaki, Kazuhiko

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目的:观察体外扩增的骨髓内皮祖细胞对局灶性脑缺血再灌注损伤的早期作用。在纤维连接蛋白包被的培养皿上培养10~14d后,在大脑中动脉闭塞90min后经动脉注入2.5×10(5)细胞的内皮祖细胞。结果:在24小时和48小时,内皮祖细胞显著减少脑梗塞体积和神经功能缺失评分。损伤后2小时给予内皮祖细胞并不能减少梗塞体积,但可减轻24小时的神经功能缺陷。给予内皮祖细胞显著减少24小时缺血区髓过氧化物酶免疫反应细胞的数量,并在48小时增加局部皮质血流量。在缺血侧和软脑膜动脉内皮层周围可见内皮祖细胞。结论:体外扩增的骨髓内皮祖细胞减少了急性局灶性脑缺血再灌注损伤的脑梗塞体积和神经功能障碍,至少部分是由于内皮功能障碍的减轻所致。
OBJECTIVE: This study aimed to examine early effects of ex vivo-expanded bone marrow-derived endothelial progenitor cells (EPCs) on focal cerebral ischemia-reperfusion injury.METHODS: EPCs were obtained from mononuclear cells of autologous bone marrow of a rat. After culture on fibronectin-coated dishes for 10 to 14 days, 2.5 X 10(5) cells of EPCs were administered transarterially after 90 minute occlusion of the middle cerebral artery.RESULTS: Administration of EPCs significantly reduced both the infarct volume and the scores of neurological deficits at 24 and 48 hours. EPCs administered 2 hours after insult did not reduce infarct volume, but attenuated neurological deficits at 24 hours. Administration of EPCs significantly reduced the number of myeloperoxidase-immunoreactive cells in the ischemic lesion at 24 hours and increased regional cortical blood flow at 48 hours. EPCs were observed in the ischemic hemisphere and around the endothelial layer of the pial arteries. Most of them expressed endothelial nitric oxide synthase.CONCLUSION: Administration of ex vivo-expanded bone marrow-derived EPCs reduced infarct volume and neurological deficits in acute focal brain ischemia-reperfusion injury caused, at least in part, by attenuation of endothelial dysfunction.