title: GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat.
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.
authors.affiliation: Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Preclinical Medicine Research Center, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Chaoxian
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Neurobiology, Southwest Medical University, Zhongshan Road, Luzhou, Sichuan 646000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Anatomy and Neurobiology, Tongji University School of Medicine, Siping Road, Shanghai 200092, China.
authors.forename: Qionglan
authors.initials: Q
authors.lastname: Yuan