title: Synergistic and Superimposed Effect of Bone Marrow-Derived Mesenchymal Stem Cells Combined with Fasudil in Experimental Autoimmune Encephalomyelitis.
abstract: Bone marrow-derived mesenchymal stem cells (MSCs) are the ideal transplanted cells of cellular therapy for promoting neuroprotection and neurorestoration. However, the optimization of transplanted cells and the improvement of microenvironment around implanted cells are still two critical challenges for enhancing therapeutic effect. In the current study, we observed the therapeutic potential of MSCs combined with Fasudil in mouse model of experimental autoimmune encephalomyelitis (EAE) and explored possible mechanisms of action. The results clearly show that combined intervention of MSCs and Fasudil further reduced the severity of EAE compared with MSCs or Fasudil alone, indicating a synergistic and superimposed effect in treating EAE. The addition of Fasudil inhibited MSC-induced inflammatory signaling TLR-4/MyD88 and inflammatory molecule IFN-γ, IL-1β, and TNF-α but did not convert M1 microglia to M2 phenotype. The delivery of MSCs enhanced the expression of glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) compared with that of Fasudil. Importantly, combined intervention of MSCs and Fasudil further increased the expression of BDNF and GDNF compared with the delivery of MSCs alone, indicating that combined intervention of MSCs and Fasudil synergistically contributes to the expression of neurotrophic factors which should be related to the expression of increased galactocerebroside (GalC) compared with mice treated with Fasudil and MSCs alone. However, a lot of investigation is warranted to further elucidate the cross talk of MSCs and Fasudil in the therapeutic potential of EAE/multiple sclerosis.
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Jing-Wen
authors: JW
authors: Yu
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Yan-Hua
authors: YH
authors: Li
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Guo-Bin
authors: GB
authors: Song
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Jie-Zhong
authors: JZ
authors: Yu
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Chun-Yun
authors: CY
authors: Liu
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Jian-Chun
authors: JC
authors: Liu
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China.
authors: Hai-Fei
authors: HF
authors: Zhang
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Wan-Fang
authors: WF
authors: Yang
authors: "2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors: Qing
authors: Q
authors: Wang
authors: Neurological Institute, Tianjin Medical University General Hospital of Tianjin Medical University, Tianjin, China.
authors: Ya-Ping
authors: YP
authors: Yan
authors: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. bgxiao@shmu.edu.cn.
authors: Bao-Guo
authors: BG
authors: Xiao
authors: Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, China. macungen2001@163.com.|"2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China. macungen2001@163.com.
authors: Cun-Gen
authors: CG
authors: Ma
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D005699:Galactosylceramides; D051100:Glial Cell Line-Derived Neurotrophic Factor; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D047428:Protein Kinase Inhibitors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C002454:galactocerebroside; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil
keywords: Experimental autoimmune encephalomyelitis; Fasudil; Mesenchymal stem cells; Rho kinase inhibitor