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Int J Stem Cells. 2019 Nov 30;12(3):440-448. doi: 10.15283/ijsc18139.

Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis.

Author information

1
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
2
Department of Technology, Stem Cell Medicine Engineering & Technology Research Center of Inner Mongolia, Huhhot, Inner Mongolia, China.
3
Department of Research and Development, Beijing Jingmeng Stem Cell Technology CO., LTD, Beijing, China.
4
Health Examination Center, Tongliao City Hospital, Tongliao, Inner Mongolia, China.
5
Department of Medicine, Chifeng Cancer Hospital, Chifeng, Inner Mongolia, China.

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:

Colitis; Exosome; Immunosuppressive effect; Mesenchymal stromal cells; Serum free

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