JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (1): 35-41.doi: 10.3969/j.issn.1674-8115.2021.01.006

• Basic research • Previous Articles     Next Articles

Therapeutic effects of the combination of fasudil and C-C chemokine receptor type 5-transducted mesenchymal stem cells on experimental autoimmune encephalomyelitis

Yan-hua LI1(), Ya-ping YAN2, Xiao-qin LIU1, Guo-ping XI1, Guo-bin SONG1, Bao-guo XIAO3, Cun-gen MA1,4()   

  1. 1.Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science, Shanxi Datong University, Datong 037009, China
    2.College of Life Science, Shaanxi Normal University, Xi'an 710062, China
    3.Institute of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China
    4.The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Chinese Medicine, Research Center of Neurobiology, Shanxi University of Chinese Medicine, Jinzhong 030619, China
  • Online:2021-01-28 Published:2021-02-22
  • Contact: Cun-gen MA E-mail:278912829@qq.com;macungen2001@163.com
  • 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)

Abstract: Objective

·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).

Methods

·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.

Results

·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).

Conclusion

·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.

Key words: fasudil, C-C chemokine receptor type 5 (CCR5), mesenchymal stem cell (MSC), experimental autoimmune encephalomyelitis (EAE)

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