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

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 encephal...

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Main Authors: Xiaoqing Gao, Li Deng, Yun Wang, Ling Yin, Chaoxian Yang, Jie Du, Qionglan Yuan
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1431349
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author Xiaoqing Gao
Li Deng
Yun Wang
Ling Yin
Chaoxian Yang
Jie Du
Qionglan Yuan
author_facet Xiaoqing Gao
Li Deng
Yun Wang
Ling Yin
Chaoxian Yang
Jie Du
Qionglan Yuan
author_sort Xiaoqing Gao
collection DOAJ
description 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.
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spelling doaj-art-c0b09d270eaf454faaee20d6f5b998b82025-08-20T02:19:22ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/14313491431349GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in RatXiaoqing Gao0Li Deng1Yun Wang2Ling Yin3Chaoxian Yang4Jie Du5Qionglan Yuan6Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaDepartment of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaDepartment of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaPreclinical Medicine Research Center, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaDepartment of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaDepartment of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, ChinaDepartment of Anatomy and Neurobiology, Tongji University School of Medicine, Siping Road, Shanghai 200092, ChinaMultiple 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.http://dx.doi.org/10.1155/2016/1431349
spellingShingle Xiaoqing Gao
Li Deng
Yun Wang
Ling Yin
Chaoxian Yang
Jie Du
Qionglan Yuan
GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
Stem Cells International
title GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
title_full GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
title_fullStr GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
title_full_unstemmed GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
title_short GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat
title_sort gdnf enhances therapeutic efficiency of neural stem cells based therapy in chronic experimental allergic encephalomyelitis in rat
url http://dx.doi.org/10.1155/2016/1431349
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