The Immunosuppressive Effect of Mesenchymal Stromal Cells on B Lymphocytes Is Mediated by Membrane Vesicles
The Immunosuppressive Effect of Mesenchymal Stromal Cells on B Lymphocytes Is Mediated by Membrane Vesicles
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DOI：
10.3727/096368911x582769
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Muraca, Maurizio
中科院分区：
文献类型：
--
作者：
Budoni, Manuela;Fierabracci, Alessandra;Muraca, Maurizio
间充质基质细胞的免疫调节特性越来越受到关注，并扩大了临床应用，但其作用的可重复性是有争议的，其潜在机制尚未完全阐明。我们研究了膜囊泡的转移，这是最近认识到的细胞间通讯途径，可能是间充质基质细胞和B淋巴细胞之间相互作用的介体。在CpG刺激的外周血单核细胞共培养系统中，间充质基质细胞表现出强烈的剂量依赖性抑制B细胞增殖和分化。我们观察到，这些效果可以完全再现的膜囊泡分离间充质基质细胞培养上清液中的剂量依赖性的方式。接下来，我们通过流式细胞术和共聚焦显微镜分析评估了荧光标记的膜囊泡在特定细胞亚型内的定位。在外周血单核细胞培养中，发现膜囊泡与刺激的B淋巴细胞相关，但与其他细胞表型（T淋巴细胞、树突状细胞、自然杀伤细胞）无关。这些结果表明，来自间充质基质细胞的膜囊泡是对B淋巴细胞的免疫抑制作用的输送者。这些颗粒应作为免疫抑制剂替代亲本细胞进行进一步评估，在标准化，安全性和可行性方面可能具有优势。
The immunomodulatory properties of mesenchymal stromal cells are the subject of increasing interest and of widening clinical applications, but the reproducibility of their effects is controversial and the underlying mechanisms have not been fully clarified. We investigated the transfer of membrane vesicles, a recently recognized pathway of intercellular communication, as possible mediator of the interaction between mesenchymal stromal cells and B lymphocytes. Mesenchymal stromal cells exhibited a strong dose-dependent inhibition of B-cell proliferation and differentiation in a CpG-stimulated peripheral blood mononuclear cell coculture system. We observed that these effects could be fully reproduced by membrane vesicles isolated from mesenchymal stromal cell culture supernatants in a dose-dependent fashion. Next, we evaluated the localization of fluorescently labeled membrane vesicles within specific cell subtypes both by flow cytometry and by confocal microscopy analysis. Membrane vesicles were found to be associated with stimulated B lymphocytes, but not with other cell phenotypes (T lymphocytes, dendritic cells, natural killer cells), in peripheral blood mononuclear cell culture. These results suggest that membrane vesicles derived from mesenchymal stromal cells are the conveyors of the immunosuppressive effect on B lymphocytes. These particles should be further evaluated as immunosuppressive agents in place of the parent cells, with possible advantages in term of standardization, safety, and feasibility.