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, 12 (3), 440-448

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


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

Zhi Jie Ma et al. Int J Stem Cells.


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.

Conflict of interest statement

Potential Conflict of Interest

The authors have no conflicting financial interest.


Fig. 1
Fig. 1
Characteristics of MSC-Exo. (A) Transmission electron microscopy analysis of exosomes secreted by UCMSCs cultured in defined medium. Scale bar: 50 nm. (B) CD63, CD9, and CD81 expressions in MSC-Exo were detected by western blotting. (C) The size distribution profile of MSC-Exo.
Fig. 2
Fig. 2
MSC-Exo possessed a certain degree of immunosuppressive capability in vitro. The concentrations of the pro-inflammatory cytokines (A) IFN-γ, (B) TNF-α and (C) IL-1β and anti-inflammatory cytokines (D) TGF-β1 and (E) IL-10 were measured in the supernatant of PBMCs treated with different levels of MSC-Exo for 72 h. (F) The proliferation of PBMCs was evaluated after culture with different levels of MSC-Exo. Bars indicate means±SD. n=5; *p<0.05, **p<0.01, and ***p<0.001.
Fig. 3
Fig. 3
MSC-Exo or MSCs alleviated clinical symptom in DSS-induced colitis mice. (A) Scheme of study design. (B) Body weight was monitored daily. (C) Disease activity index (DAI) scores were measured on day 10. Bars indicate means±SD. n=5~8; *p<0.05 and **p<0.01.
Fig. 4
Fig. 4
MSC-Exo or MSCs alleviated colonic damage in DSS-induced colitis mice. (A) Representative images of colon length. (B) Colon length was quantitatively analyzed. (C) Representative H&E staining, bar=100 μm. (D) Corresponding severity score was determined. Bars indicate means± SD. n=5~8; *p<0.05.
Fig. 5
Fig. 5
MSC-Exo or MSCs reduced the infammatory state in DSS-induced colitis mice. The concentrations of the pro-inflammatory cytokines (A) IFN-γ, (B) TNF-α, (C) IL-6 and (D) IL-17 and anti-inflammatory cytokines (E) IL-10 and (F) TGF-β1 in colonic protein extracts were measured by ELISA. Bars indicate mean±SD, n=5~8; *p<0.05, **p<0.01 and ***p<0.001.

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