[Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis].
OBJECTIVE
To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE).


METHODS
An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation.


RESULTS
CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes.


CONCLUSIONS
Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.
Lu
Zheng-qi
ZQ
Department of Neurology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China. lzq1828@yahoo.com.cn
Hu
Xue-qiang
XQ
Zhu
Can-sheng
CS
Zheng
Xue-ping
XP
Wan
Dun-jing
DJ
Liu
Ran-yi
RY
Huang
Bi-jun
BJ
Huang
Wen-lin
WL
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D017154:Stromal Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D020934:Ciliary Neurotrophic Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma