Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis.

Xiaoqing Gao,Li Deng,Guangbi Fan,Chaoxian Yang,Guangqiang Hu,Junying Du

doi:10.1155/2016/3081939

Abstract

The present study investigates whether transplantation of NSCs treated with T3 alone (T3/NSCs), or in conjunction with GDNF gene (GDNF-T3/NSCs), provides a better therapeutic effect than NSCs for chronic EAE. EAE rats were, respectively, injected with NSCs, T3/NSCs, GDNF-T3/NSCs, and saline at 10 days and sacrificed at 60 days after EAE immunization. The three cell grafted groups showed a significant reduction in clinical scores, inflammatory infiltration, and demyelination compared with the saline-injected group, and among the cell grafted groups, the reduction in GDNF-T3/NSCs group was the most notable, followed by T3/NSCs group. Grafted T3/NSCs and GDNF-T3/NSCs acquired more MAP2, GalC, and less GFAP in brain compared with grafted NSCs, and grafted GDNF-T3/NSCs acquired most MAP2 and least GalC among the cell grafted groups. Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFαR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group. In conclusion, T3/NSCs grafting, especially GDNF-T3/NSCs grafting, provides a better neuroprotective effect for EAE than NSCs transplantation.

Highlights

Chronic experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), is an autoimmune disease in the CNS characterized by extensive plaques or lesions throughout grey and white matter, with loss of myelin and myelinating cells as well as damage to axons and neurons [1]
Our study shows that grafting Neural stem cells (NSCs), T3/NSCs, and GDNFT3/NSCs into rats subjected to EAE significantly improved functional outcome compared with control group
T3/NSCs and Glial cell line-derived neurotrophic factor (GDNF)-T3/NSCs groups reduced significantly inflammatory infiltrations and demyelination compared with NSCs group, and greater reductions in GDNF-T3/NSCs group were observed compared with the T3/NSCs group

Summary

Introduction

Chronic experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), is an autoimmune disease in the CNS characterized by extensive plaques or lesions throughout grey and white matter, with loss of myelin and myelinating cells as well as damage to axons and neurons [1]. Driving neurons and oligodendrocytes commitment and development of transplanted NSCs should largely promote the success of transplantation therapy for EAE. NSCs from EAE animals show a strong limitation in oligodendrocyte generation, which is completely recovered by T3 treatment [7]. Glial cell line-derived neurotrophic factor (GDNF) has been proved to have a potent neuroprotective effect on various neuronal damage [11,12,13] and has an ability to promote axon regeneration and myelination after spinal cord injury [14]. GDNF gene modified-fibroblasts transplantation promoted significant axons regeneration and remyelination of regenerating axons following spinal cord transection injury [15].

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Results

Conclusion