Immunomodulatory Effects of Mesenchymal Stem Cells in a Murine Model of TNBS-Induced Colitis

ABSTRACT

PURPOSE: Mesenchymal stem cells (MSCs) are surfacing as a new method of treatment for various diseases that have poor outcome with drug treatments. In this study, we investigated the effects of MSCs in a murine intestinal inflammation model mimicking human Crohn's disease (CD) using 2,4,5-trinitrobenzene sulfonic acid (TNBS). METHODS: Colitis was induced by rectal administration of 2 mg of TNBS in 35% ethanol as experimental group compared to control group. Histological changes, surface molecules of T and B cells of the spleen and blood, and cytokine production (IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, and IL-12) were determined among 3 groups comprised of control group, TNBS group and TNBS/MSC group. RESULTS: In the mice treated with MSCs, there was a decrease in the wasting disease process and inflammatory histopathological changes. There was also a decrease in pro-inflammatory T-helper 1 (Th1) cytokines IFN-gamma and IL-12 and T-helper 2 (Th2) cytokine IL-4. Anti-inflammatory cytokine IL-10 increased in mice treated with MSCs compared to colitic mice. The blood CD4+CD25+ T-regulatory cells also increased and splenic CD19 B-cells decreased. CONCLUSION: The results of this study suggest that MSCs may have a therapeutic effect in controlling the Th1 and Th2 mediated immune response in patients with CD and aid in tissue regeneration.