P332 The efficacy of tonsil-derived mesenchymal stem cell in acute murine colitis model

Abstract

Background: Mesencymal stromal cells (MSCs) are multipotent progenitor cells originally derived from bone marrow and currently under investigation for the treatment of inflammatory bowel disease such as Crohn’s disease. Clinical application of bone marrow-derived MSC is difficult due to morbidity and low isolation efficiency, therefore MSC sources have diversified. We evaluate the therapeutic effect of tonsil-derived mesenchymal stem cells (TMSCs), a newly developed source of MSC in acute murine colitis model for the first time. Methods: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis group (DSS + saline), low dose TMSC group (DSS + TMSCs 1x106), and high dose TMSC group (DSS + TMSCs 2x106). For the induction of acute colitis, mice were treated with 3% DSS in drinking water for 7 days. TMSCs were administered to the treated mice via intraperitoneal route on day 3. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic inflammatory grading. Multiple inflammatory cytokines (IL-6, IFN-g, TNF-a, IL-1b, IL-12p40, and COX-2) were examined using RT-PCR. Results: The TMSC group showed lower DAI, lower shortening of the colon length, and lower histopathologic grading compared with the DSS colitis group, with no significant statistical difference (p = 0.133, p = 0.073, p = 0.103). The degree of changes did not show a dose-dependent increase. The expressions of IL-6 and IFN-g in colonic tissue were lower in the TMSC group, but with no significant difference (p = 0.136, p = 0.143). Other inflammatory cytokines did not show difference between DSS group and TMSC group. Conclusions: The significant therapeutic effect of TMSC in acute murine colitis model assessed by DAI, histopathologic grading, colon length, and inflammatory cytokines was not proved. However, there was some trend in TMSC group that may be the expected therapeutic effect. This study is the first trial applied TMSC to treat acute murine colitis model as a new source of cell-based therapy. To elucidate the exact effects of TMSC, further evaluation will be needed using other various experimental environment such as other drug injection route, drug dose, and other cytokines in large scale.