Open AccessNasal delivery of Fasudil‐modified immune cells exhibits therapeutic potential in experimental autoimmune encephalomyelitis
Author(s) -
Guo ShangDe,
Liu ChunYun,
Yu JingWen,
Chai Zhi,
Wang Qing,
Mi XiTing,
Song GuoBin,
Li YanHua,
Yang PengWei,
Feng Ling,
Xiao BaoGuo,
Ma CunGen
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13111
Subject(s) - fasudil , experimental autoimmune encephalomyelitis , myelin oligodendrocyte glycoprotein , medicine , immunology , pharmacology , encephalomyelitis , inflammation , multiple sclerosis , rho associated protein kinase , chemistry , signal transduction , biochemistry
Summary Aim Multiple sclerosis (MS) is a relapsing‐remitting inflammatory demyelinating disease that requires long‐term treatment. Although Rho kinase inhibitor Fasudil shows good therapeutic effect in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, certain side effects may limit its clinical use. This study aimed at observing the therapeutic potential of Fasudil‐modified encephalitogenic mononuclear cells (MNCs) via nasal delivery in EAE and exploring possible mechanisms of action. Methods Experimental autoimmune encephalomyelitis was induced with myelin oligodendrocyte glycoprotein 35‐55 in C57BL/6 mice, and encephalitogenic MNCs were treated with Fasudil in vitro. Mice received 3 × 10 6 cells/10 μL per nasal cavity on day 3 and 11 postimmunization, respectively. Results Fasudil‐modified MNCs reduced clinical severity of EAE, improved demyelination, and decreased inflammatory cells in spinal cords. Immunohistochemical results indicated that CD4 + T cells and CD68 + macrophages were barely detected in Fasudil‐MNCs group. Fasudil‐modified MNCs decreased CD4 + IFN‐γ + and CD4 + IL‐17 + T cells, increased CD4 + IL‐10 + T cells, restrained M1 markers CD16/32, CCR7, IL‐12, CD8a, enhanced M2 markers CD206, CD200, CD14 in spleen. Fasudil‐modified MNCs inhibited the activation of inflammatory signaling p‐NF‐kB/P38, accompanied by the decrease of COX‐2 and the increase of Arg‐1 in spinal cord, as well as the reduction of IL‐17, TNF‐α, IL‐6 and the elevation of IL‐10 in cultured supernatant of splenocytes. Fasudil‐modified MNCs enhanced the levels of neurotrophic factors BDNF and NT‐3 in spinal cord. Conclusion Our results indicate that intranasal delivery of Fasudil‐modified MNCs have therapeutic potential in EAE, providing a safe and effective cell therapeutic strategy to MS and/or other related disorders.