[Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis]

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Dec;29(12):2355-61.
[Article in Chinese]

Abstract

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.

Conclusion: 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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Animals
  • Bone Marrow Cells / metabolism*
  • Ciliary Neurotrophic Factor / biosynthesis
  • Ciliary Neurotrophic Factor / genetics
  • Ciliary Neurotrophic Factor / 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

Substances

  • Ciliary Neurotrophic Factor
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma