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

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

Affiliations
  • 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. stemcells@foxmail.com
  • 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.

Abstract

BACKGROUND AND OBJECTIVE
S: 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.

Keyword

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

MeSH Terms

Animals
Colitis*
Colon
Cytokines
Down-Regulation
Exosomes*
In Vitro Techniques
Inflammation
Inflammatory Bowel Diseases
Interleukin-10
Mesenchymal Stromal Cells*
Mice
Up-Regulation
Weight Loss
Cytokines
Interleukin-10
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