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P013. Mesenchymal stem cells injection reduces colitis severity and does not increase colitis-associated colon cancer risk in mice

F. Scaldaferri IV1, A. Puglisi1, L. Lopetuso1, M. Pizzoferrato1, V. Gerardi1, V. Cufino2, V. Petito1, G. Andrisani1, E. Stigliano2, V. Arena1, A. Papa1, A. Sgambato1, A. Gasbarrini1

1Catholic University of Rome, Internal Medicine Department, Gastroenterology Division, Rome, Italy; 2Catholic University of Rome, Pathology Department, Rome, Italy

Introduction and Objectives: Mesenchymal stem cells (AMSC) are potent immune regulators, proposed for local and systemic use in human and experimental IBD. Cancer studies found stem cell to be involved in mechanisms of cancer induction and progression, warning the use of stem cell in clinical condition associated to increased cancer risk, such as ulcerative colitis. Despite this, very few information exist on whether and how the use of mesenchymal stem cell influences cancer induction in chronic colitis.

Aims and Methods: Aim of this study was to evaluate the potential therapeutic effect of AMSC in a murine model of colon cancer associated to chronic colitis. AMSC were isolated from adipose tissue of C57BL/6 mice, analyzed for mesenchymal stem cell markers and for adipocyteand osteogenicdifferentiation. C57BL/6 mice were injected intraperitoneally with 7 mg/Kg of azoxymethane (AOM) and then exposed to 3 cycles of 2.5% DextranSodium Sulfate (DSS), given for 7 days in tap water. 400.000 AMSC were injected twice intraperitoneallyat day 1 of I and II DSS cycle; control mice received buffer alone. Body weight, occult blood test and stool consistency were measured twice a week and used to calculate the Disease Activity Index (DAI) to assess severity of colitis; survival was expressed as %. Mice were sacrificed at week 10 and colon was analyzed macroscopically and microscopically for number of cancer and degree of inflammation.

Results: AMSC retained stem cells properties as they differentiated into adipocytes and osteocytes, and expressed low levels of CD90 together with higher levels of SCA-1 and CD49e. In vivo, AMSC injection significantly reduced DAI in treated mice compared to controls, especially during the first 6 weeks of treatment. AMSC treated mice showed also a lower body weight loss and a better survival rate compared to controls (100% vs 65%). At macroscopic analysis, AMSC treated mice showed a reduced rate of colon cancer development compared to controls (33% vs 67%). However the number of tumors per mouse did not differ significantly among mice which actually developed cancer (1.7 vs 1.5 tumors/mouse).

Conclusion: In conclusion, AMSC exerted a immune-modulatory effect in vivo, by decreasing the severity of colitis in mouse. Furthermore, AMSC did not increase cancer risk in this model, suggesting that their anti-inflammatory effects may contra-balance their pro-carcinogenetic potential, even in pre-cancer condition such as chronic colitis. Further analysis are required to better define mechanisms of action underlying these findings.