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Therapeutic effects of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells on experimental autoimmune encephalomyelitis
Online published: 2021-02-22
Supported by
Funding Information] Research Project Supported by Shanxi Scholarship Council of China(HGKY2019089);International Key Research & Development Cooperation Plan of Datong(2019123);Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases(201805D111009)
·To study the therapeutic effect of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells (CCR5-MSCs) on experimental autoimmune encephalomyelitis (EAE).
·The mice immunized with myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG35-55) were randomly divided into EAE model group (intraperitoneal injection of normal saline), fasudil intervention group (intraperitoneal injection of fasudil), CCR5-MSCs intervention group (nasal administration of CCR5-MSCs), and fasudil combined with CCR5-MSCs intervention group (intranasal administration of CCR5-MSCs, intraperitoneal injection of fasudil), with 8 mice in each group. The clinical score of EAE mice were checked every day after MOG35-55 immunization. All mice were sacrificed on the 28th day after the first immunization. The myelin integrity was observed by luxol fast blue staining. The production of neural stem cells and oligodendrocyte precursor cells in spinal cord tissue was analyzed by immunofluorescence staining. The expressions of neurotrophic factors in spinal cord tissue were detected by Western blotting.
·Compared with the other three groups, the clinical score of EAE in the fasudil combined with CCR5-MSCs intervention group was lower (P=0.000, P=0.007, P=0.005), and the demyelination was reduced (P=0.000, P=0.009, P=0.008). The production of neural stem cells and oligodendrocyte precursor cells in spinal cord tissue was increased (all P=0.000), and the expression of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 increased (all P=0.000).
·Fasudil combined with CCR5-MSCs is more effective than fasudil or CCR5-MSCs in the treatment of EAE, which may be related to the induction of remyelination and the production of the neurotrophic factor.
Yan-hua LI , Ya-ping YAN , Xiao-qin LIU , Guo-ping XI , Guo-bin SONG , Bao-guo XIAO , Cun-gen MA . Therapeutic effects of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells on experimental autoimmune encephalomyelitis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(1) : 35 -41 . DOI: 10.3969/j.issn.1674-8115.2021.01.006
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