GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat.
GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat.
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GDNF 提高神经干细胞疗法对大鼠慢性实验性过敏性脑脊髓炎的治疗效率
DOI：
10.1155/2016/1431349
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发表时间：
2016
影响因子：
4.3
通讯作者：
Yuan Q
中科院分区：
文献类型：
--
作者：
Gao X;Deng L;Wang Y;Yin L;Yang C;Du J;Yuan Q
多发性硬化（MS）是中枢神经系统的自身免疫性疾病。目前用于MS的免疫调节药物不能有效预防进行性神经功能衰退。神经干细胞（Neural stem cells，NSCs）移植可促进实验性变态反应性脑脊髓炎（experimental allergic encephalomyelitis，EAE）动物模型的修复和功能恢复，胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）也具有促进轴突再生和再生轴突髓鞘形成的能力。本研究将GDNF基因修饰的神经干细胞（GDNF/NSCs）和天然神经干细胞分别移植于EAE免疫后10 d和60 d的大鼠侧脑室，观察GDNF是否能增强NSCs对EAE的治疗作用。我们发现，神经干细胞显着减少临床症状，GDNF基因修饰进一步促进功能恢复。GDNF/NSCs比NSCs更能抑制脑组织炎症反应，并提高髓鞘的密度。GDNF/NSCs的存活率明显高于移植NSCs。移植的GDNF/NSCs与NSCs相比，分化为更多的神经元和少突胶质细胞。此外，GDNF/NSCs组大鼠少突胶质细胞系细胞的mRNA表达显著高于NSCs组大鼠。这些结果表明GDNF增强了基于神经干细胞的治疗EAE的疗效。
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.