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Immunomodulatory effects of mesenchymal stromal cells-derived exosome

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Abstract

The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors’ bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

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Acknowledgments

This study was supported by Important Special Subject Foundation of Guangzhou (201400000003-1; 201400000003-4) and Key Project of Natural Science Foundation of Guangdong Province (2014A0303110066), National Natural Science Foundation of China (81570107).

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    Authors and Affiliations

    1. Southern Medical University, Guangzhou, 510515, China

      Wancheng Chen, Yukai Huang, Jiaochan Han, Lili Yu, Yanli Li, Ziyuan Lu, Hongbo Li, Chenyan Shi, Fengqi Duan & Yang Xiao

    2. Department of Hematology, General Hospital of Guangzhou Military Command, Guangzhou, 510010, China

      Wancheng Chen, Hongbo Li, Zenghui Liu, Chenyan Shi, Fengqi Duan & Yang Xiao

    3. Department of Hematology, The Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics-Guangdong Province), Guangzhou, 510630, China

      Yang Xiao

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    1. Wancheng Chen
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    All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

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    Wancheng Chen and Yukai Huang have contributed equally to this work.

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    Chen, W., Huang, Y., Han, J. et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res 64, 831–840 (2016). https://doi.org/10.1007/s12026-016-8798-6

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    • DOI: https://doi.org/10.1007/s12026-016-8798-6

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