Use of Mesenchymal Stem Cells in Inflammatory Bowel Disease

Chronic inappropriate mucosal immune activation, due to aberrant host interactions with intestinal microbiota, is at the heart of inflammatory bowel disease (IBD) pathogenesis. Currently, there is no cure for IBD and mainstays of therapy are limited to non-cell specific immunosuppression/immunomodulation, antibiotics and surgery. Advanced ulcerative colitis patients cost approximately 10,000JD in therapy per year with 12.4% of patients presenting with rectal bleeding in Jordan being diagnosed with ulcerative colitis. The role of MSCs in immune modulation is well established in many diseases. However, the therapeutic potential of MSCs directly injected into the inflamed large intestine or parentally has not been fully investigated. Injected MSCs may modulate the IBD immune response particularly lymphoid T-cell and neutrophil activities. While a variety of immune cells contribute to the disease, increased neutrophil activity is associated with greater frequency and severity of active inflammation, as well as increased colitis associated cancer risk. MPOx can transform lipids and polyamines into reactive carbonyl species (RCS) capable of modifying proteins and DNA, altering cell signalling pathways. Finally, MPOx is reported as a useful tool in screening and risk stratification of human ulcerative colitis and colorectal cancer. Inhibiting MPOx in an accelerated preclinical mouse model did reduce incidence and tumor load resulting from gut inflammation. Additionally, in similar preclinical models others have reported that MSC transplantation reduces colitis severity and inflammatory markers including MPOx activity. Even in the absence of the well-known MSC T-cell immune modulation, disease activity indices and MPOx activity were reduced in these models. In addition to following traditional clinical outcomes, Reseachers will analyze gut immune responses, specifically neutrophil MPOx activity along with other IBD immune markers.