Synergistic and Superimposed Effect of Bone Marrow-Derived Mesenchymal Stem Cells Combined with Fasudil in Experimental Autoimmune Encephalomyelitis
Synergistic and Superimposed Effect of Bone Marrow-Derived Mesenchymal Stem Cells Combined with Fasudil in Experimental Autoimmune Encephalomyelitis
复制标题
骨髓间充质干细胞联合法舒地尔治疗实验性自身免疫性脑脊髓炎的协同叠加作用
DOI：
10.1007/s12031-016-0819-3
复制
发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Ma C. G.
中科院分区：
文献类型：
--
作者：
Yu J. W.;Li Y. H.;Song G. B.;Yu J. Z.;Liu C. Y.;Liu J. C.;Zhang H. F.;Yang W. F.;Wang Q.;Yan Y. P.;Xiao B. G.;Ma C. G.
骨髓间充质干细胞（MSCs）是促进神经保护和神经修复的细胞治疗的理想移植细胞。然而，移植细胞的优化和植入细胞周围微环境的改善仍然是提高治疗效果的两个关键挑战。本研究观察了MSCs联合法舒地尔对实验性自身免疫性脑脊髓炎（EAE）小鼠模型的治疗作用，并探讨了其可能的作用机制。结果清楚地表明，与单独的MSC或法舒地尔相比，MSC和法舒地尔的组合干预进一步降低了EAE的严重程度，表明在治疗EAE中的协同和叠加效应。法舒地尔的加入抑制了MSC诱导的炎症信号TLR-4/MyD 88和炎症分子IFN-γ、IL-1β和TNF-α，但未将M1小胶质细胞转化为M2表型。与法舒地尔相比，MSCs的递送增强了胶质细胞源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF）的表达。重要的是，与单独递送MSC相比，MSC和法舒地尔的组合干预进一步增加了BDNF和GDNF的表达，表明MSC和法舒地尔的组合干预协同地有助于神经营养因子的表达，与单独用法舒地尔和MSC处理的小鼠相比，神经营养因子的表达应该与增加的半乳糖苷（GalC）的表达相关。然而，需要进行大量研究以进一步阐明MSC和法舒地尔在EAE/多发性硬化的治疗潜力中的串扰。
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.
登录
查看更多内容
影响因子：
4.3
作者：
Cefalo MG;Carai A;Miele E;Po A;Ferretti E;Mastronuzzi A;Germano IM
通讯作者：
Germano IM
DOI：
10.1177/1352458508091370
发表时间：
2008-07
期刊：
Multiple Sclerosis
影响因子：
--
作者：
A. Wilkins;N. Scolding
通讯作者：
A. Wilkins;N. Scolding
影响因子：
5.6
作者：
Urdzíková LM;Růžička J;LaBagnara M;Kárová K;Kubinová Š;Jiráková K;Murali R;Syková E;Jhanwar-Uniyal M;Jendelová P
通讯作者：
Jendelová P
影响因子：
--
作者：
Karussis, Dimitrios;Karageorgiou, Clementine;Vaknin-Dembinsky, Adi;Gowda-Kurkalli, Basan;Gomori, John M.;Kassis, Ibrahim;Bulte, Jeff W. M.;Petrou, Panayiota;Ben-Hur, Tamir;Abramsky, Oded;Slavin, Shimon
通讯作者：
Slavin, Shimon
DOI：
10.1055/s-0034-1399353
发表时间：
2015-04
期刊：
Fortschritte der Neurologie-Psychiatrie
影响因子：
--
作者：
R. Patejdl;Penner Ik;T. Noack;U. K. Zettl
通讯作者：
R. Patejdl;Penner Ik;T. Noack;U. K. Zettl