Retrovirus delivered neurotrophin-3 promotes survival, proliferation and neuronal differentiation of human fetal neural stem cells in vitro
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- 作者：Haixia Lu ; Minjie Li ; Tusheng Song ; Yihua Qian ; Xinli Xiao ; Xinlin Chen ; Pengbo Zhang ; Xinshun Feng ; Terence Parker ; Yong Liu
- 关键词：Neural stem cells ; Neurotrophin-3 ; Retrovirus ; Survival ; Proliferation ; Differentiation
- 刊名：Brain Research Bulletin
- 出版年：2008
- 出版时间：22 October 2008
- 年：2008
- 卷：77
- 期：4
- 页码：158-164
- 全文大小：996 K
文摘
Poor survival and insufficient neuronal differentiation are the main obstacles to neural stem cell (NSC) transplantation therapy. Genetic modification of NSCs with neurotrophins is considered a promising approach to overcome these difficulties. In this study, the effects on survival, proliferation and neuronal differentiation of human fetal NSCs (hfNSCs) were observed after infection by a neurotrophin-3 (NT-3) recombinant retrovirus. The hfNSCs, from 12-week human fetal brains formed neurospheres, expressed the stem cell marker nestin and differentiated into the three main cell types of the nervous system. NT-3 recombinant retrovirus (Retro-NT-3) infected hfNSCs efficiently expressed NT-3 gene for at least 8 weeks, presented an accelerated proliferation, and therefore produced an increased number of neurospheres and after differentiation in vitro, contained a higher percentage of neuronal cells. Eight weeks after infection, 37.9 ± 4.2 % of hfNSCs in the Retro-NT-3 infection group expressed the neuronal marker, this was significantly higher than the control and mock infection groups. NT-3 transduced hfNSCs also displayed longer protruding neurites compared with other groups. Combined these results demonstrate that NT-3 modification promote the survival/proliferation, neuronal differentiation and growth of neurites of hfNSCs in vitro. This study proposes recombinant retrovirus mediated NT-3 modification may provide a promising means to resolve the poor survival and insufficient neuronal differentiation of NSCs.