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

• Published in: Neuroscience letters 2008-10, Vol.444 (3), p.227-230
• Main Authors: Zhang, Zi-heng, Wang, Ren-zhi, Li, Gui-lin, Wei, Jun-ji, Li, Zhao-jian, Feng, Ming, Kang, Jun, Du, Wan-chen, Ma, Wen-bin, Li, Yong-ning, Yang, Yi, Kong, Yan-guo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cerebral ischemia; Embryonic Stem Cells - transplantation; Functional recovery; Fundamental and applied biological sciences. Psychology; Gene transduction; Genetic Therapy; Genetic Vectors; Humans; Ischemic Attack, Transient - physiopathology; Ischemic Attack, Transient - therapy; Lentivirus - genetics; Male; Medical sciences; Neural stem cell; Neurology; Neurons - metabolism; Neurons - transplantation; Neurotrophin 3 - biosynthesis; Neurotrophin 3 - genetics; Rats; Rats, Sprague-Dawley; Recovery of Function; Transplantation; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.08.049

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.