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* = Presenting author

P025 Tonsil-derived mesenchymal stem cell ameliorate intestinal fibrosis in chronic murine colitis model

E. M. Song*1, S.-A. Jung1, S.-E. Kim1, K. E. Lee1, J. Y. Chang1, H. M. Son1, M. S. Ryu1, Y. H. Joo1, C. H. Tae1, C. M. Moon1, H.-K. Jung1, K.-N. Shim1, I. H. Jo2, Y. S. Yu2

1Ewha Woman’s University School of Medicine, Department of Internal Medicine, Ewha Medical Research Institute, Seoul, South Korea, 2Ewha Woman’ University School of Medicine, Department of Molecular Medicine, Ewha Medical Research Institute, Seoul, South Korea

Background

Tonsil-derived mesenchymal stem cells (T-MSCs), a newly established source of MSC, have many advantages including shorter doubling time, high differentiating capacity, and mixed chimerism property from multiple donors. In a previous study, we revealed that inflammatory symptoms including weight loss, bloody diarrhoea, and shortening of colon length were ameliorated by T-MSC injection in acute and chronic colitis model. However, histological improvement was not obvious. The present work is aimed at evaluating the possible effect of T-MSCs on intestinal fibrosis in chronic murine colitis model.

Methods

In the study, 7-to-8-week-old C57BL/6 mice were randomly assigned to 3 groups: normal control, DSS colitis group (DSS + saline), and T-MSC group (DSS + T-MSC 1x106 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 via intraperitoneal route on day 6 and day 16. The severity of the colitis was assessed by the disease activity index (DAI), colon length, and histologic grading. Colon specimens were stained with Masson’s trichrome to visualise the collagen fibres. Fibrosis was scored by a blinded observer based on the scoring criteria considering the increased level of collagen fibre and the percent involvement of fibrosis.

Results

In the DSS colitis group, marked infiltration of inflammatory cells, loss of crypts, and reduction of goblet cells and focal ulcerations were denoted mainly at mucosa and submucosa. Transmural inflammation was occasionally detected. But, unlike DAI showing significant improvement in the T-MSC group (3.4 vs 2.3, p < 0.01), histologic improvement was not evident (8.4 vs 8.7, p = 0.128). Masson’s trichrome staining demonstrated increased deposits of collagen in mucosa and submucosa of DSS colitis group. In some colon specimen, collagen fibrils were increased in the muscularis propria. The T-MSC group showed more sparse deposition of collagen fibres in submucosal level, compared with the DSS colitis group. The fibrosis score was significantly lowered in the T-MSC group compared with the DSS colitis group (2.71 vs 5.67, p < 0.05).

Conclusion

In our study, intraperitoneal administration of T-MSC reduced the intestinal fibrosis in chronic murine colitis model. Whether T-MSC have indeed the therapeutic potential for intestinal fibrosis warrants further evaluation with large scale.