Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis.
- Author:
Zheng-qi LU
1
;
Xue-qiang HU
;
Can-sheng ZHU
;
Xue-ping ZHENG
;
Dun-jing WAN
;
Ran-yi LIU
;
Bi-jun HUANG
;
Wen-lin HUANG
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; metabolism; Animals; Bone Marrow Cells; metabolism; Ciliary Neurotrophic Factor; biosynthesis; genetics; therapeutic use; Encephalomyelitis, Autoimmune, Experimental; therapy; Female; Genetic Therapy; Interferon-gamma; blood; Mice; Mice, Inbred C57BL; Random Allocation; Stromal Cells; metabolism; T-Lymphocytes; immunology; Transfection; Tumor Necrosis Factor-alpha; blood
- From: Journal of Southern Medical University 2009;29(12):2355-2361
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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).
METHODSAn 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.
RESULTSCNTF 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.
CONCLUSIONTransplantation 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.