Disparate Effects of Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis and Cuprizone-Induced Demyelination
Disparate Effects of Mesenchymal Stem Cells in Experimental Autoimmune Encephalomyelitis and Cuprizone-Induced Demyelination
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DOI：
10.1371/journal.pone.0139008
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发表时间：
2015-09-25
期刊：
影响因子：
3.7
通讯作者：
Whartenby, Katharine A.
中科院分区：
文献类型：
--
作者：
Glenn, Justin D.;Smith, Matthew D.;Whartenby, Katharine A.
间充质干细胞（MSC）是多效性细胞，对多种疾病具有潜在的治疗益处。由于其免疫调节特性，它们已被用于治疗自身免疫性疾病，例如以脱髓鞘为特征的多发性硬化症（MS）。 MSC 周围的微环境被认为会影响其分化和表型，进而影响疗效。因此，我们试图分别使用 MOG(35-55) 实验性自身免疫性脑脊髓炎 (EAE) 和铜宗介导的脱髓鞘模型，剖析 MSC 在 T 细胞介导和非 T 细胞介导的环境中对中枢神经系统 (CNS) 疾病的不同影响的潜力。由于 MS 和 EAE 的发病机制被认为是由产生 IFN γ (T(H)1) 和产生 IL-17A (T(H)17) 效应 CD4+ T 细胞介导的，因此我们研究了 MSC 对这两个关键致病细胞群发育的影响。尽管MSC抑制了T(H)17细胞的激活和效应功能，但它们并不影响T(H)1激活，而是增强了T(H)1效应功能，最终对EAE没有影响。在非 T 细胞介导的铜宗脱髓鞘模型中，MSC 给药具有积极作用，与对照组相比，MSC 治疗的小鼠大脑中髓磷脂丰度总体增加。这些结果凸显了间充质干细胞作为治疗自身免疫性疾病的生物治疗工具的潜在变异性，以及需要进一步研究间充质干细胞在不同微环境中的多方面功能以及多样性背后的机制。
Mesenchymal stem cells (MSCs) are pleiotropic cells with potential therapeutic benefits for a wide range of diseases. Because of their immunomodulatory properties they have been utilized to treat autoimmune diseases such as multiple sclerosis (MS), which is characterized by demyelination. The microenvironment surrounding MSCs is thought to affect their differentiation and phenotype, which could in turn affect the efficacy. We thus sought to dissect the potential for differential impact of MSCs on central nervous system (CNS) disease in T cell mediated and non-T cell mediated settings using the MOG(35-55) experimental autoimmune encephalomyelitis (EAE) and cuprizone-mediated demyelination models, respectively. As the pathogeneses of MS and EAE are thought to be mediated by IFN gamma-producing (T(H)1) and IL-17A-producing (T(H)17) effector CD4+ T cells, we investigated the effect of MSCs on the development of these two key pathogenic cell groups. Although MSCs suppressed the activation and effector function of T(H)17 cells, they did not affect T(H)1 activation, but enhanced T(H)1 effector function and ultimately produced no effect on EAE. In the non-T cell mediated cuprizone model of demyelination, MSC administration had a positive effect, with an overall increase in myelin abundance in the brain of MSC-treated mice compared to controls. These results highlight the potential variability of MSCs as a biologic therapeutic tool in the treatment of autoimmune disease and the need for further investigation into the multifaceted functions of MSCs in diverse microenvironments and the mechanisms behind the diversity.