29 HUMAN BONE MARROW DERIVED MESENCHYMAL STEM CELLS MEDIATE IMMUNOSUPPRESSION IN EXPERIMENTAL CROHN’S DISEASE BY SECRETING PROSTAGLANDIN E2 AND REPROGRAMMING MACROPHAGES TO AN ANTI-INFLAMMATORY PHENOTYPE

Abstract Background Locally injected mesenchymal stem cells (MSCs) are now an approved therapy in European Union for perianal Crohn’s disease (CD) fistulas, however, clinical studies have shown limited efficacy of systemic MSC therapy for luminal CD. Thus, we studied the SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestine (SI) inflammation for treatment with human bone marrow derived MSC (hMSC). We previously reported that hMSCs injected intraperitoneally (i.p) into SAMP resulted in histologic, mucosal and radiologic healing (Dave M et al. Gastroenterology 154 (6), S-438). Aims and Methods The aim of this study was to determine the mechanism(s) by which hMSCs mediate immunosuppression in SAMP. hMSCs were transduced with lentivirus vector containing shRNA for COX-2 (hMSCshCOX-2) to knockdown secretion of Prostaglandin E2 (PGE2) and lentivirus with scrambled shRNA was used as control (hMSC-S control). Results Using NanoString immune cell profiling assay, SAMP mice treated with hMSC i.p had increased abundance of macrophages and decreased abundance of lymphocytes in the SI. In MLRs set up with T lymphocytes from SAMP mice, hMSCs profoundly suppressed T cell proliferation in a dose dependent manner as measured by [3H] thymidine incorporation (95% CI of difference: 8,573 – 14,335 cpm; ANOVA P