Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation
Annual rept. 5 Aug 2014-4 Aug 2015
TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
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The overall objective of this proposal is to evaluate the therapeutic efficacy of human, bone marrow-derived mesenchymal stem cells hMSCs in a mouse model of inflammatory bowel disease IBD. As mentioned in my previous report, we encountered an unexpected problem with our mouse model of IBD following our relocation to TTUHSC. We have spent the last 2 years developing and characterizing a new model that has a much incidence of disease than what we observed following our relocation to TTUHSC. Unfortunately, this situation delayed the start of the studies outlined in Tasks 1 and 2. Nevertheless, we now have the studies outlined in Task 1 currently underway. We present new and exciting data demonstrating that the inflammation observed in our re-derived mouse model of IBD is characterized by the infiltration of much larger numbers of myeloid cells into the inflamed colon compared to our original model. In addition, we have made great progress in developing a more immunologicallyrelevant in vitro system to assess immuno-suppressive activity and mechanisms of suppression of hMSCs Task 3. This antigenspecific, in vitro model more closely mimics the cellular and immunological interactions that occur in our in vivo mouse model of IBD. Surprisingly we find that hMSCs are much less effective at suppressing antigen-specific proliferation of mouse T cells compared to the immunosuppressive effects of mouse regulatory T cells or mouse MSCs. These data, together with our previous data demonstrating that hMSCs attenuate IBD in mice suggest that suppression of disease may not be due to suppression of T cell proliferation in vivo. We care currently exploring whether hMSCs suppress inflammatory cytokine generation by mouse T cells.
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