Transplantation of neural stem cells modified by human neurotrophin-3 promotes functional recovery after transient focal cerebral ischemia in rats

被引:58
作者
Zhang, Zi-heng [1 ]
Wang, Ren-zhi [1 ]
Wang, Ren-zhi [1 ]
Li, Gui-lin [1 ]
Wei, Jun-ji [1 ]
Li, Zhao-jian [1 ]
Feng, Ming [1 ]
Kang, Jun [1 ]
Du, Wan-chen [1 ]
Ma, Wen-bin [1 ]
Li, Yong-ning [1 ]
Yang, Yi [1 ]
Kong, Yan-guo [1 ]
机构
[1] Beijing Union Med Coll Hosp, Peking Union Med Coll, Dept Neurosurg, Beijing 100730, Peoples R China
基金
中国国家自然科学基金;
关键词
Cerebral ischemia; Neural stem cell; Gene transduction; Transplantation; Functional recovery;
D O I
10.1016/j.neulet.2008.08.049
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The study tested the hypothesis that transplantation of human neurotrophin-3 (hNT-3) over-expressing neural stem cells (NSCs) into rat striatum after a severe focal ischemia would promote functional recovery. Rat NSCs, transduced by Flag-tagged hNT-3 gene mediated by lentiviral vector(LV), were transplanted into the striatum ipsilateral to the injury of adult rats 7 days after 2-h occlusion of the middle cerebral artery (MCAO). From 3 days to 2 weeks after transplantation, the modified cells (NSCs-hNT3, as defined by Flag immunofluorencence staining) that survived the transplantation procedures could secrete significantly higher levels of neurotrophin-3 protein in the graft sites than controls (P < 0.001). Furthermore, the rats that accepted NSCs-hNT3 exhibited enhanced functional recovery on neurological and behavioral tests, compared with controlled animals transplanted with saline or untransduced NSCs. This study suggests: (I) LV is an ideal vector to transduce foreign gene into the NSCs; (2) modified NSCs could carry therapeutic genes to disease tissues and express effectively: (3) modified cells Could survive in the ischemic brains and continue to secrete neurotrophin-3 abundantly for over 2 weeks, which might have values for enhancing functional recovery after stroke. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:227 / 230
页数:4
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