Neurotrophin-3 gene transduction of mouse neural stem cells promotes proliferation and neuronal differentiation in organotypic hippocampal slice cultures.
BACKGROUND
The transplantation of neural stem cells (NSCs) has been accepted as a promising therapeutic strategy for central nervous system disorders. However, the beneficial effect of NSC transplantation upon functional recovery is limited due to the unfavorable microenvironment (niche) at the site of trauma or degenerative disease in the brain. Combination of transplantation of NSCs with neurotrophins may overcome the hurdles of impaired cell survival and neuronal differentiation.


METHODS
In the current study, the neurotrophin-3 (NT-3) gene was transduced into cultured mouse embryonic cortical NSCs via an AAV vector (NSC-NT-3). The effect of NT-3 over-expression on cell proliferation and differentiation in NSCs was observed by immunohistochemistry, cell culture and organotypic hippocampal slice cultures.<br />


RESULTS
The characteristics of self-renewal and multiple differentiation of NSCs were well-preserved. Cells in the NSC-NT-3 group proliferated faster and differentiated into more β-tubulin III-positive neurons compared to the control group in vitro. Furthermore, cells in the NSC-NT-3 group survived in a significantly higher percentage and undertook neuronal differentiation preferably in organotypic hippocampal slice cultures.


CONCLUSIONS
Our results suggest that the transduction of NT-3 into NSCs could effectively promote NSCs survival, proliferation, and neuronal differentiation in vitro without change of the stemness of NSCs. This work also offers evidence to better understand the safety and efficiency of combined treatment with NT-3 and NSCs for the central nervous system disorders.
Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, Xi'an Jiaotong University College of Medicine, Xi'an, PR China.
Hai-xia
HX
Lu
Zhi-ming
ZM
Hao
Qian
Q
Jiao
Wu-ling
WL
Xie
Jun-feng
JF
Zhang
Yi-fei
YF
Lu
Min
M
Cai
Yuan-yuan
YY
Wang
Zhi-qian
ZQ
Yang
Terry
T
Parker
Yong
Y
Liu
D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D000229:Dependovirus; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*
D020933:Neurotrophin 3