Intraperitonial/ Subcutaneous delivery of fit autologous Mesenchymal Stromal cells effectively cure DSS induced colitis

Abstract

Background & Aim Background Bone marrow derived Mesenchymal stromal cells (BM-MSCs) with their excellent regenerative and immunomodulatory function, offer great potential for diverse clinical application. However, the success rate of advanced clinical trials has not been proven to be as promising as pre-clinical animal data in a wide array of disease models. Proper knowledge of the biological and pharmacological aspects of MSC based therapy is required to meet the medical demand of human clinical trials. AIM To execute a controlled, side-by-side comparison of the effects of delivery route, metabolic fitness and immune compatibility on dwell time and therapeutic efficacy of BM-MSC in mouse model of colitis. Methods, Results & Conclusion Methods/procedures Here we have compared the efficacy of 1) allogenic vs. autologous 2) metabolically active vs. inactive and 3) IP/IV/SC route of BM-MSC transplantation in a model of DSS-induced colitis mice, Finally, using in vivo optical imaging, we identified the most effective mode of BM-MSC application by tracking the bio-distribution and survival of bioluminescent BM-MSC. Main findings BM-MSC delivered by intraperitoneal or subcutaneous route is equivalently efficacious and superior than intravenous route of administration in reduction of colitis severity. Metabolically active BM-MSC supports prolonged cell survival as well as shows best biological activity. Immunocompetent colitis mice reject allogenic MHC-mismatched MSC. Conclusion Culture-rescued, metabolically active autologous BM-MSC achieves maximal potency if administered via IP or SC route into mouse model of colitis.