Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

Abstract

Abstract : The overall objective of this proposal is to evaluate the therapeutic efficacy of human, bone marrow-derived mesenchymal stem cells (MSCs) in a well-characterized mouse model of inflammatory bowel disease (IBD). Shortly after my relocation from LSU Health Sciences Center (LSUHSC) to my current position at Texas Tech Health Sciences Center (TTUHSC), we encountered an unexpected problem with our mouse model of IBD. We found that the incidence of intestinal inflammation in these mice was only 30-40% compared to our 15 year historical incidence of 85% we observed at LSUHSC. Following a year of investigations, we identified the problem and were successful in reestablishing the model with an incidence of 95%. Although these investigations significantly delayed the start of the studies outlined in Task 1, we were able to begin experiments to ascertain the immuno-suppressive activity of human MSCs in our new and improved mouse model of IBD. These studies are currently ongoing. In addition, we made substantial progress in developing a more immunologically-relevant in vitro system to assess suppressive activity and mechanisms of MSCs that more closely models the cellular and immunological interactions that are thought to occur in our mouse model of IBD in vivo. Furthermore, we present exciting new data demonstrating that activation of MSCs with pro-inflammatory cytokines that are known to be overproduced in mouse and human IBD, induces the dramatic up-regulation of several different immuno-suppressive mediators. Finally, we present new data that utilizes a novel, highly sensitive and quantitative method for simultaneously measuring the homing of human MSCs to several different mouse tissues during the development of chronic gut inflammation.