title: Transplantation of neural stem cells modified by human neurotrophin-3 promotes functional recovery after transient focal cerebral ischemia in rats.
abstract: 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: (1) 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.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Zi-Heng
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Ren-Zhi
authors.initials: RZ
authors.lastname: Wang
authors.forename: Ren-Zhi
authors.initials: RZ
authors.lastname: Wang
authors.forename: Gui-Lin
authors.initials: GL
authors.lastname: Li
authors.forename: Jun-Ji
authors.initials: JJ
authors.lastname: Wei
authors.forename: Zhao-Jian
authors.initials: ZJ
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Feng
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Du
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Ma
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yan-Guo
authors.initials: YG
authors.lastname: Kong