Differential and transferable modulatory effects of mesenchymal stromal cell-derived extracellular vesicles on T, B and NK cell functions.
Differential and transferable modulatory effects of mesenchymal stromal cell-derived extracellular vesicles on T, B and NK cell functions.
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DOI：
10.1038/srep24120
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发表时间：
2016-04-13
影响因子：
4.6
通讯作者：
Krampera M
中科院分区：
文献类型：
--
作者：
Di Trapani M;Bassi G;Midolo M;Gatti A;Kamga PT;Cassaro A;Carusone R;Adamo A;Krampera M
间充质基质细胞（MSC）是多能细胞、免疫调节干细胞，其目前用于再生医学和许多炎性疾病的治疗，这归功于它们通过分泌大量可溶性因子显著影响组织微环境的能力。最近，几个研究小组报道了MSC分泌瘤中存在细胞外囊泡（EV），显示了它们在不同疾病动物模型中的有益作用。在这里，我们使用了一种标准化的方法来剖析MSC衍生的EV对普通外周血单核细胞和纯化的T、B和NK细胞的免疫调节作用。我们在这里描述的第一次：i。EV介导的免疫抑制的程度与免疫效应细胞的EV摄取之间的直接相关性，这是在用炎性细胞因子引发MSC后进一步放大的现象; ii.通过从致敏的MSC获得的EV在静息MSC中诱导对T细胞增殖的免疫抑制特性，而对T细胞分裂没有任何直接抑制作用。我们的结论是，使用可重复和验证的测定不仅可用于表征MSC衍生EV的作用机制，而且还能够证明EV作为治疗人类炎症性疾病的替代无细胞疗法的潜在用途。
Mesenchymal stromal cells (MSCs) are multipotent cells, immunomodulatory stem cells that are currently used for regenerative medicine and treatment of a number of inflammatory diseases, thanks to their ability to significantly influence tissue microenvironments through the secretion of large variety of soluble factors. Recently, several groups have reported the presence of extracellular vesicles (EVs) within MSC secretoma, showing their beneficial effect in different animal models of disease. Here, we used a standardized methodological approach to dissect the immunomodulatory effects exerted by MSC-derived EVs on unfractionated peripheral blood mononuclear cells and purified T, B and NK cells. We describe here for the first time: i. direct correlation between the degree of EV-mediated immunosuppression and EV uptake by immune effector cells, a phenomenon further amplified following MSC priming with inflammatory cytokines; ii. induction in resting MSCs of immunosuppressive properties towards T cell proliferation through EVs obtained from primed MSCs, without any direct inhibitory effect towards T cell division. Our conclusion is that the use of reproducible and validated assays is not only useful to characterize the mechanisms of action of MSC-derived EVs, but is also capable of justifying EV potential use as alternative cell-free therapy for the treatment of human inflammatory diseases.