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