GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat.

Xiaoqing Gao,Chaoxian Yang,Li Deng,Ling Yin,Yun Wang,Qionglan Yuan,Jie Du

doi:10.1155/2016/1431349

Xiaoqing Gao, Chaoxian Yang + Show 5 more

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https://doi.org/10.1155/2016/1431349

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Abstract

Multiple sclerosis (MS) is an autoimmune disease in the CNS. The current immunomodulating drugs for MS do not effectively prevent the progressive neurological decline. Neural stem cells (NSCs) transplantation has been proven to promote repair and functional recovery of experimental allergic encephalomyelitis (EAE) animal model for MS, and glial cell line-derived neurotrophic factor (GDNF) has also been found to have capability of promoting axonal regeneration and remyelination of regenerating axons. In the present study, to assess whether GDNF would enhance therapeutic effect of NSCs for EAE, GDNF gene-modified NSCs (GDNF/NSCs) and native NSCs were transplanted into each lateral ventricle of rats at 10 days and rats were sacrificed at 60 days after EAE immunization. We found that NSCs significantly reduced the clinical signs, and GDNF gene-modification further promoted functional recovery. GDNF/NSCs more profoundly suppressed brain inflammation and improved density of myelin compared with NSCs. The survival of GDNF/NSCs was significantly higher than that of transplanted NSCs. Transplanted GDNF/NSCs, in contrast to NSCs, differentiated into more neurons and oligodendrocytes. Moreover, the mRNA expression of oligodendrocyte lineage cells in rats with GDNF/NSCs was significantly increased compared to rats with NSCs. These results suggest that GDNF enhances therapeutic efficiency of NSCs-based therapy for EAE.

Highlights

Experimental allergic encephalomyelitis (EAE), most commonly used animal model of multiple sclerosis (MS), is an autoimmune disease in the central nervous system (CNS) induced and mediated by myelin-reactive T cells responses against myelin antigens [1]
Neurospheres were plated in coverslips with medium containing 10% fetal bovine serum (FBS) without basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and N2 supplement for 7 days
Our study showed that grafting neural stem cells (NSCs) and glial cell line-derived neurotrophic factor (GDNF)/NSCs into rats subjected to EAE significantly improved function compared with control group, and GDNF/NSCs group showed better efficacy

Summary

Introduction

Experimental allergic encephalomyelitis (EAE), most commonly used animal model of multiple sclerosis (MS), is an autoimmune disease in the central nervous system (CNS) induced and mediated by myelin-reactive T cells responses against myelin antigens [1]. Lower survival rate [6] and low levels of differentiation of oligodendrocytes [7] and neurons [8] after transplantation limit the therapeutic efficacy of NSCs. Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been demonstrated to have neuroprotection against a variety of neuronal insults [9, 10]. Our previous studies have shown that GDNF gene-modified NSCs provided more efficient neuroprotection for rats subjected to stroke than native NSCs [14]. Here, we speculate that GDNF may enhance therapeutic efficiency of NSCs therapy for EAE. The purpose of this study is to investigate whether GDNF gene-modified NSCs provide a more efficacious treatment for EAE than NSCs alone

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