TLR3 Preconditioning Enhances the Therapeutic Efficacy of Umbilical Cord Mesenchymal Stem Cells in DSS-induced Colitis (VAC8P.995)

Background and Aim: Mesenchymal stem cells (MSCs) have attracted much attention since exert anti-inflammatory and immunomodulatory effects. Recently, diverse studies have been showed that the stimulation of specific toll-like receptors affects the immunomodulatory properties of MSCs. The aim of this work was to evaluate the effects of TLR preconditioning on therapeutic efficacy of umbilical cord MSCs (UC-MSCs) in a murine model of acute colitis. Methods: C57BL/6 mice were exposed to 2,5 % dextran sulfate sodium (DSS) in drinking water. At days 1 and 3 were injected intraperitoneally with 1 x 106 of UC-MSCs or TLR3 and TLR4-preconditioning UC-MSCs. We evaluated Clinical signs of disease, body weights daily, plasma cytokines levels, colon length and histological changes. Results: The infusion of TLR3-preconditioned UC-MSCs significantly ameliorated the clinical and histopathologic severity of DSS-induced colitis compared with wild type UC-MSCs or TLR4-preconditioned UC-MSCs. In contrast, infusion of TLR4-preconditioned UC-MSCs significantly increased the clinical signs of disease, colon shortening and histological disease index. Conclusions: These results suggest that the immunomodulatory properties of UC-MSCs can be differentially modulated by TLR agonists. Also, these data showed that the short in-vitro TLR3-preconditioning enhances the therapeutic efficacy of UC-MSCs, which can be very useful for treatment or amelioration of proinflammatory diseases.