Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis
- Author:
Zhi Jie MA
1
;
Yun Hong WANG
;
Zhi Gang LI
;
Ying WANG
;
Bing Yao LI
;
Hui Yan KANG
;
Xiao Yun WU
Author Information
- Publication Type:Original Article
- Keywords: Mesenchymal stromal cells; Colitis; Immunosuppressive effect; Serum free; Exosome
- MeSH: Animals; Colitis; Colon; Cytokines; Down-Regulation; Exosomes; In Vitro Techniques; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Mesenchymal Stromal Cells; Mice; Up-Regulation; Weight Loss
- From:International Journal of Stem Cells 2019;12(3):440-448
- CountryRepublic of Korea
- Language:English
- 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.
