Project Summary/Abstract: Cell therapy is an innovative and non-toxic regenerative approach for the treatment of inflammatory and degenerative disorders. Mesenchymal Stromal/Stem Cells (MSCs) are widely being tested as cellular and regenerative therapy and in some countries, it is already approved as standard clinical care for the management of inflammatory bowel disease associated complications. Specifically, Perianal fistula (PF) is a serious complication of Crohn’s Disease (CD) which substantially affects the quality of life of those patients. Treatment options are limited and are not highly effective. MSCs derived from adipose tissue has been approved in Europe for the treatment of complex PF in patients with CD. Although this stem cell therapy is showing efficacy, side effects such as anal abscess, proctalgia, and variations in treatment responses are common which could be due to the allogeneic nature of this cell therapy. The current unmet is the development of an autologous cell therapy strategy with enhanced potency and safety for the treatment of PF. We hypothesize that MSCs derived from the rectum of patients with CD display robust immunosuppressive and regenerative properties that can be used as an autologous cellular therapy. We also hypothesize that rectum derived MSCs’ potency can be further improved with appropriate inflammatory cue mediated preactivation, and thus they can function amidst confounding factors. In the present preclinical research phase, we aim to characterize the potency of rectum derived MSCs from patients with CD. Mercer University School of Medicine’s mission is to educate students to become future physicians and serve rural and underserved regions of Georgia. Involvement of students in this Research Enhancement Award Program will bring exposure and help them to apply cellular therapy in rural health care. The results of this study can inform a second-generation cell therapy approach not only for the management of PF but also for bowel inflammation.