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Title: Intraperitoneal administration of mesenchymal stem cells ameliorates acute dextran sulfate sodium-induced colitis by suppressing dendritic cells
Authors: Nikolić A.
Simovic Markovic, Bojana
Gazdic, Marina
Randall Harrell C.
Fellabaum C.
Jovicic, Nemanja
Djonov, Valentin
Arsenijevic, Nebojsa
Lukic, Miodrag
Stojković M.
Volarevic, Vladislav
Journal: Biomedicine and Pharmacotherapy
Issue Date: 1-Apr-2018
Abstract: © 2018 Elsevier Masson SAS 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.
Type: Article
DOI: 10.1016/j.biopha.2018.02.060
ISSN: 07533322
SCOPUS: 85042253114
Appears in Collections:Faculty of Medical Sciences, Kragujevac
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