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P009. The long-term therapeutic effect of bone marrow-derived mesenchymal stem cells in a dextran sulfate sodium-induced murine colitis

H.J. Lee, H.W. Jang, J.-H. Kwon, K.J. Lee, S.J. Park, S.P. Hong, J.H. Cheon, W.H. Kim, T.I. Kim, Institute of Gastroenterology, Yonsei University College of Medicine, Department of Internal Medicine, Seoul, Korea, Republic of

Background

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to have immunoregulatory functions, especially in immune-mediated diseases including inflammatory bowel disease (IBD). Although systemic infusion of BM-MSCs revealed beneficial effects in experimental colitis models, the mechanisms are not fully understood yet and most of the studies focused on the prevention and improvement of acute gut inflammation after injection of BM-MSCs. Therefore, in this study, we investigated the long-term therapeutic effect of BM-MSCs especially in chronic colitis induced by dextran-sulfate sodium (DSS).

Methods

Chronic colitis was induced by administering 3% DSS in the drinking water in a cyclic manner (3 cycles). BM-MSCs were injected intravenously into the DSS-treated mice three times during first cycle DSS administration. On day 33, therapeutic effect was evaluated by clinicopathologic profiles as body weight, colon length, and histological scoring. Inflammatory mediators such as IL10, TGF beta, and TNF alpha in the inflamed colon were measured by real-time polymerase chain reaction (PCR).

Results

Systemic infusion of BM-MSCs significantly ameliorated the clinical and histopathological severity of colitis. In addition, BM-MSCs treatment showed a sustained therapeutic effect throughout the third cycle of DSS administration. Administration of DSS in three cycles resulted in three peak of colitis, characterized by sustained weight loss and bloody diarrhea, but body weight restoration was significantly promoted in BM-MSC treated mice. In microscopic examination, DSS colitis mice treated with BM-MSCs had less inflammatory infiltrates, extent, and loss of crypt structure, compared to DSS colitis mice. Anti-inflammatory cytokine levels of IL10 showed significant increase in inflamed colon of BM-MSC treated DSS colitis mice, compared to DSS colitis mice.

Conclusion

We found that systemic infusion of BM-MSCs at the disease onset could exert long-term immunosuppressive effects and, therefore, BM-MSCs treatment could be an effective means to treat chronic colitis in mice.