Intraperitoneal administration of mesenchymal stem cells ameliorates acute dextran sulfate sodium-induced colitis by suppressing dendritic cells

• Published in: Biomedicine & pharmacotherapy 2018-04, Vol.100, p.426-432
• Main Authors: Nikolic, Aleksandar, Simovic Markovic, Bojana, Gazdic, Marina, Randall Harrell, C., Fellabaum, Crissy, Jovicic, Nemanja, Djonov, Valentin, Arsenijevic, Nebojsa, L Lukic, Miodrag, Stojkovic, Miodrag, Volarevic, Vladislav
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Colitis - chemically induced; Colitis - immunology; Colitis - therapy; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dextran Sulfate - toxicity; DSS-induced colitis; Injections, Intraperitoneal; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mice; Mice, Inbred C57BL
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.02.060

Dendritic cells (DCs) have important pathogenic role in the induction and progression of ulcerative colitis (UC), but their role in mesenchymal stem cells (MSCs)-mediated suppression of colon injury and inflammation is not revealed. By using dextran sodium sulfate (DSS)-induced colitis, a well-established murine model of UC, we examined effects of MSCs on phenotype and function of colon infiltrating DCs. Clinical, histological, immunophenotypic analysis and passive transfer of MSCs-primed DCs were used to evaluate capacity of MSC to suppress inflammatory phenotype of DCs in vivo. Additionally, DCs:MSCs interplay was also investigated in vitro, to confirmed in vivo obtained findings. Intraperitoneally administered MSCs (2 × 106) significantly reduced progression of DSS-induced colitis and reduced serum levels of inflammatory cytokines (IL-1β, IL-12, and IL-6). Passive transfer of in vivo MSCs-primed DCs reduced severity of colitis while passive transfer of MSCs-non-primed DCs aggravated DSS-induced colitis. Through the secretion of immunomodulatory Galectin 3, MSCs, in paracrine manner, down-regulated production of inflammatory cytokines in DCs and attenuated expression of co-stimulatory and major histocompatibility complex class II molecules on their membranes. Taken together, these results indicate that MSCs achieved their beneficial effects in DSS-induced colitis by suppressing inflammatory phenotype of DCs in Gal-3 dependent manner. Therapeutic targeting of DCs by MSCs should be explored in future studies as a useful approach for the treatment of UC.