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P061 The efficacy of tonsil-derived mesenchymal stem cell in chronic murine colitis model

E.M. Song*1, S.-A. Jung1, S.-E. Kim1, Y.H. Joo1, Y.S. Yu2, C.H. Tae1, C.M. Moon1, H.-K. Jung1, K.-N. Shim1, I.H. Jo2, M.S. Ryu1, J.-M. Lee1

1Ewha Womans University School of Medicine, Department of Internal Medicine, Ewha Medical Research Institute, Seoul , Korea, Republic of, 2Ewha Womans University School of Medicine, Department of Molecular Medicine, Ewha Medical Research Institute, Seoul, Korea, Republic of

Background

Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including inflammatory bowel disease (IBD). Tonsil-derived mesenchymal stem cells (T-MSC), a newly-established source of MSC, have many advantages including shorter doubling time, retaining stemness, high differentiating capacity and immune modulatory activity. IBD undergoes a chronic relapsing-remitting condition rather than acute one, here, we aimed to examine whether T-MSC have the therapeutic effect in chronic mice model of IBD.

Methods

Seven to eight week old C57BL/6 mice were randomly assigned to 3 groups: normal control, DSS colitis group (DSS + saline), low-dose T-MSC group (DSS + T-MSC 1x106 per injection) and high-dose T-MSC group (DSS+ T-MSC 2x106 per injection). For the induction of chronic colitis, the mice were treated with 1.5 % DSS for 5 days followed by 5 days of drinking water continuously for 3 cycles (30 days). T-MSC was administered to the treated mice via intraperitoneal route on day 6 and day 16. The severity of the colitis was assessed by the disease activity index (DAI) on every day, colon length, histologic grading and inflammatory cytokines such as IL-6, TNF- σ , IL-10.

Results

Mice with DSS induced chronic colitis suffered pancolitis in 43.5%. 72.9% of mice colon specimen showed infiltration of inflammatory cells at submucosal level or more. The colon length was significantly shortened in the DSS colitis group compared with the normal control group (64.3 ± 5.5 vs 82.7 ± 6.7 mm, p < 0.01). The T-MSC treated group showed less shortening of colon compared to the DSS colitis group (68.7 ± 4.2 vs 64.3 ± 5.5, p = 0.057). The injection of T-MSC improved the DAI at D7 (3.4 ± 1.4 vs 4.8 ± 1.5, p = 0.016), but, the improvement was not significant at D14, D21 and D28. The histopathologic grading appeared to be lower in the T-MSC group than the DSS colitis group, but, there was no statistically significant difference (9.2 ± 1.9 vs 8.0 ± 0.9, p = 0.086). The expressions of IL-6, TNF- σ , IL-10 did not differ between the DSS colitis and T-MSC groups.

Conclusion

In our study, intraperitoneal administration of T-MSC reduced the shortening of colon length, disease activity and histopathological inflammation in chronic murine colitis model, but with no statistically significant differences. Whether T-MSC has indeed the therapeutic potential for chronic colitis warrants further evaluation with large scale.