Laboratory of Cellular and Molecular Immunology, Faculty of Medicine, University of Los Andes, 750000 Santiago, Chile.
Laboratory of Integrative and Molecular Physiology, Faculty of Medicine, University of Los Andes, 750000 Santiago, Chile.
Stem Cells Int. 2015;2015:140170. doi: 10.1155/2015/140170. Epub 2015 Mar 9.
Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect of MSCs administration at different disease stages in experimental autoimmune encephalomyelitis (EAE). Classical and atypical scores of EAE, associated with Th1 and Th17 response, respectively, and also Treg lymphocytes, were evaluated. MSCs administration at the onset (EAE+MSConset) induced an important amelioration of the clinical signs and less lasting effect at the peak of EAE (EAE+MSCpeak). No effect was observed when MSCs were applied after EAE stabilization (EAE+MSClate). Surprisingly, EAE atypical signs were detected in EAE+MSCpeak and EAE+MSClate mice. However, no correlation was found in Th17/Th1 ratio. Interestingly, regardless of time administration, MSCs significantly reduced IL-6 and also T-bet, RORγT, and Foxp3 mRNA levels in brain samples of EAE mice. The downregulation of IL-6 could restore the well-functioning of the blood-brain barrier of EAE mice, correlated with a decreased number of brain infiltrating leukocytes. These results suggest that the inflammatory status is important to be considered for administering MSCs in autoimmune pathologies, leading to a further research to clarify the effect of MSCs for multiple sclerosis.
间充质干细胞（MSCs）具有强大的免疫抑制和再生特性，使其成为治疗自身免疫性疾病的一种新疗法。本研究探讨了在实验性自身免疫性脑脊髓炎（EAE）的不同疾病阶段给予 MSCs 治疗的疗效。评估了经典和非典型 EAE 评分，分别与 Th1 和 Th17 反应以及 Treg 淋巴细胞相关。在 EAE 发病时给予 MSCs 治疗（EAE+MSConset）可显著改善临床症状，但在 EAE 高峰时持续效果较差（EAE+MSCpeak）。在 EAE 稳定后给予 MSCs 治疗（EAE+MSClate）则没有效果。令人惊讶的是，在 EAE+MSCpeak 和 EAE+MSClate 小鼠中检测到了 EAE 的非典型症状。然而，Th17/Th1 比值没有相关性。有趣的是，无论给予时间如何，MSCs 均可显著降低 EAE 小鼠脑组织中 IL-6 以及 T-bet、RORγT 和 Foxp3 mRNA 水平。IL-6 的下调可恢复 EAE 小鼠血脑屏障的正常功能，与脑内浸润白细胞数量减少相关。这些结果表明，在自身免疫性疾病中给予 MSCs 时，炎症状态很重要，需要进一步研究以阐明 MSCs 对多发性硬化症的作用。
