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P067. IBD98E promotes mucosal wound healing through epithelial cell proliferation in DSS-induced colitis

S. Vetrano1, M. Genua1,2, L. Petti1, P. Naccarato1, A. Gandelli1, C. Tacconi1, V. Arena3, S. D'Alessio1, S. Danese1, 1Humanitas Research Hospital, IBD Center, Rozzano, Milan, Italy, 2Humanitas Research Hospital, Medical Biotechnologies and Translational Medicine, Milano, Italy, 3Catholic University of Sacred Heart, Internal Medicine and Gastroenterology, Rome, Italy

Background

Hyaluronic acid application has been proven to be beneficial in the treatment of several diseases. Recently we have been shown that the local application of IBD98E, a new formulation in gel of Sodium hyaluronate (Na-HA), improved endoscopic and clinical outcomes in subjects with active distal UC. However, the mechanisms by which IBD98E exerts its beneficial effects are still unclear. Aim The aim of this study was to explore in vivo using an experimental model of colitis and in vitro system the therapeutic properties of IBD98E.

Methods

Acute DSS-induced colitis was performed by adding 3% DSS in drinking water in WT mice for 5 days. After this time, DSS was replaced with regular water and treated intrarectally with or without IBD98E for 6 days. Body weight, disease activity index were monitored daily, while endoscopic analysis was performed at day 0, 5, 9 and 11. At the sacrifice, a histological analysis was evaluated. Caco-2 cell line was used to test in vitro the effects of IBD98E. The cell viability and proliferation after treatment with of IBD98E were evaluated respectively by XTT test and BrdU incorporation. Wound scratch was made in the monolayers of cells incubated for 24h with epidermal growth factor (EGF) 100 ng/ml or IBD98E with or without mitomycin C treatment to inhibit cell proliferation. Photographs of the wounded area were taken at time 0 and after 24 h of the stimulation, and the percentage wound closure was calculated.

Results

Colitic mice treated with IBD98E showed faster clinical recovery, significant reduced endoscopic signs of mucosal inflammation (p < 0.01) with mild bleeding after 4 and 6 days of the treatment compared to those receiving saline. Furthermore, the histological analysis revealed a minor ulceration score in mice treated with IBD98E. In vitro, IBD98E treatment enhanced cell viability promoting proliferation. Indeed, a significant increased of BrdU incorporation (p < 0.05) as well as a wound closure (p < 0.05) was found after 24 h in the cells stimulated with IBD98E compared to untreated cells, while no significant differences were observed between IBD98E and EGF. Interestingly, no wound closure was found in response to IBD98E after pre-treatment with mitomycin C, indicating that IBD98E promotes proliferation but does not affect the migration of epithelial cells.

Conclusion

Overall these data demonstrate that sodium hyaluronate gel application is safe and favors the clinical and endoscopic outcomes of colitis reducing mucosal bleeding and promoting mucosal wound healing through proliferation of epithelial cells. Therefore IBD98E could represent a new potential treatment to promote mucosal repair in UC patients.