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Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

Authors
 HJ Kim  ;  JS Oh  ;  SS An  ;  WA Pennant  ;  S-J Gwak  ;  AN Kim  ;  PK Han  ;  DH Yoon  ;  KN Kim  ;  Y Ha 
Citation
 GENE THERAPY, Vol.19(5) : 513-521, 2012 
Journal Title
 GENE THERAPY 
ISSN
 0969-7128 
Issue Date
2012
MeSH
Animals ; Cell Hypoxia* ; Enhancer Elements, Genetic ; Erythropoietin/genetics ; Erythropoietin/metabolism ; Gene Transfer Techniques* ; Graft Survival ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Male ; Neural Stem Cells/metabolism ; Neural Stem Cells/transplantation* ; Plasmids ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley ; Recovery of Function ; Simian virus 40/genetics* ; Spinal Cord Injuries/therapy*
Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO(2), 1%) or a hypoxia-mimicking reagent (CoCl(2)) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H(2)O(2)-induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.
Full Text
http://www.nature.com/articles/gt2011137
DOI
10.1038/gt.2011.137
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Keung Nyun(김긍년)
Oh, Jin Soo(오진수)
Yoon, Do Heum(윤도흠) ORCID logo https://orcid.org/0000-0003-1452-5724
Ha, Yoon(하윤)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158324
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