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

被引：60

作者：

Zhang, Zi-heng ^{[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

来源：

NEUROSCIENCE LETTERS | 2008年 / 444卷 / 03期

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

页码：227 / 230

页数：4

共 21 条

[1]

Bharali DJ, 2005, P NATL ACAD SCI USA, V102, P11539, DOI 10.1073/pnas.0504926102

[2]

Brundin L, 2003, BRAIN PATHOL, V13, P322

[3] Robust in vivo gene transfer into adult mammalian neural stem cells by lentiviral vectors [J].