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Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis
International Journal of Stem Cells
Published online June 30, 2019;  
© 2019 Korean Society for Stem Cell Research.

Zhi Jie Ma1, Yun Hong Wang2, Zhi Gang Li3, Ying Wang4, Bing Yao Li5, Hui Yan Kang2,3, Xiao Yun Wu2,3

1Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China,
2Department of Technology, Stem Cell Medicine Engineering & Technology Research Center of Inner Mongolia, Huhhot, Inner Mongolia, China,
3Department of Research and Development, Beijing Jingmeng Stem Cell Technology CO., LTD, Beijing, China,
4Health Examination Center, Tongliao City Hospital, Tongliao, Inner Mongolia, China,
5Department of Medicine, Chifeng Cancer Hospital, Chifeng, Inner Mongolia, China
Correspondence to: Xiao Yun Wu
Department of Research and Development, Beijing Jingmeng Stem Cell Technology CO., LTD, No. 5-2 Shangdi East Road, Haidian District, Beijing 100085, China
Tel: +86-010-51557697-8230, Fax: +86-010-51557697-8099
E-mail: stemcells@foxmail.com
Received December 24, 2018; Revised April 4, 2019; Accepted April 11, 2019.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background and Objectives: The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability.
Methods: In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis.
Results and Conclusions: In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1β, and increased the secretion of anti-inflammatory cytokines TGF-β1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 μg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×106 cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.
Keywords : Mesenchymal stromal cells, Colitis, Immunosuppressive effect, Serum free, Exosome