Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses

Background & Aims Crohn's disease is a chronic disease characterized by severe T-helper (Th)1 cell–driven inflammation of the colon partially caused by a loss of immune tolerance against mucosal antigens. Mesenchymal stem cells were recently described to suppress effector T-cell responses and have therapeutic effects in some immune disorders. Here, we investigated the potential therapeutic effects of human adipose-derived mesenchymal stem cells (hASCs) in a model of inflammatory bowel disease. Methods Mice with trinitrobenzene sulfonic acid–induced colitis were treated with hASCs after onset of disease and clinical scores were evaluated. Inflammatory response was determined by measuring the levels of different inflammatory mediators in colon and serum. Th1-mediated effector responses were evaluated by determining the proliferation and cytokine profile of activated mesenteric lymph node cells. The number of regulatory T cells and the suppressive capacity on Th1 cell responses was determined. Results Systemic infusion of hASCs or murine ASCs ameliorated the clinical and histopathologic severity of colitis, abrogating body weight loss, diarrhea, and inflammation and increasing survival ( P P + CD25 + FoxP3 + regulatory T cells with suppressive capacity on Th1 effector responses in vitro and in vivo ( P Conclusions hASCs emerge as key regulators of immune tolerance and as attractive candidates for a cell-based therapy for Crohn's disease.