Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, Netherlands.
Front Immunol. 2013 Mar 4;4:49. doi: 10.3389/fimmu.2013.00049. eCollection 2013.
Mesenchymal stem cells (MSCs) show great therapeutic potential for the treatment of various immune mediated diseases, including Multiple Sclerosis (MS). Systemic administration of MSCs during experimental allergic encephalomyelitis (EAE), an animal model for MS, was shown to reduce the infiltration of T cells, B cells, and macrophages into the CNS. Whether endogenous MSCs are mobilized and potentially modulate the severity of disease is not known. Here we show that during the acute phase of EAE, MSCs numbers in the bone marrow were severely reduced, which restored to control levels during the progressive phase of the disease. The number of bone marrow MSCs inversely correlated with the number of both CD4 and CD8 T cells present in the bone marrow indicating a link between activated T cells and MSC mobilization. Analysis of CD70-transgenic mice, which have a constitutively activated immune system and elevated number of activated T cells in the bone marrow, showed severely reduced number of bone marrow MSCs. Transfer of T cells that were activated through their CD27 receptor reduced the number of bone marrow MSCs dependent on IFN-y. These data provide a mechanism by which MSCs can be mobilized from the bone marrow in order to contribute to tissue repair at a distant location.
间充质干细胞 (MSCs) 在治疗多种免疫介导的疾病方面具有巨大的治疗潜力，包括多发性硬化症 (MS)。在实验性变态反应性脑脊髓炎 (EAE) 中，MS 的动物模型中，全身给予 MSCs 可减少 T 细胞、B 细胞和巨噬细胞向中枢神经系统的浸润。内源性 MSCs 是否被动员并可能调节疾病的严重程度尚不清楚。在这里，我们表明在 EAE 的急性期，骨髓中的 MSC 数量严重减少，在疾病的进展期恢复到对照水平。骨髓中 MSC 的数量与骨髓中存在的 CD4 和 CD8 T 细胞的数量呈负相关，表明激活的 T 细胞与 MSC 动员之间存在联系。分析 CD70 转基因小鼠，其免疫系统持续激活，骨髓中活化 T 细胞数量升高，结果显示骨髓 MSC 数量严重减少。通过其 CD27 受体激活的 T 细胞的转移减少了依赖 IFN-y 的骨髓 MSC 的数量。这些数据提供了一种机制，通过该机制可以从骨髓中动员 MSC，以促进远处组织的修复。
