title: Retrovirus delivered neurotrophin-3 promotes survival, proliferation and neuronal differentiation of human fetal neural stem cells in vitro.
abstract: 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.
authors.affiliation: Institute of Neurobiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China. lhaixia71@hotmail.com
authors.forename: Haixia
authors.initials: H
authors.lastname: Lu
authors.forename: Minjie
authors.initials: M
authors.lastname: Li
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.forename: Yihua
authors.initials: Y
authors.lastname: Qian
authors.forename: Xinli
authors.initials: X
authors.lastname: Xiao
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
authors.forename: Xinshun
authors.initials: X
authors.lastname: Feng
authors.forename: Terence
authors.initials: T
authors.lastname: Parker
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D053686:Fetal Stem Cells / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016501:Neurites / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D020933:Neurotrophin 3