Study on the interactions between transplanted bone marrow-derived mesenchymal stem cells and regulatory T cells for the treatment of experimental colitis.

Accumulating evidence has established the use of mesenchymal stem cells (MSCs) as candidate cells for immunosuppressive therapy. Experimental studies have suggested that MSCs exert their immunomodulatory effects through the induction of regulatory T cells (Tregs) in vitro and in vivo. However, the interactions between MSCs and Tregs in inflammatory bowel disease (IBD) and whether MSCs can be used for the treatment of IBD remains to be elucidated. In this study, we aimed to investigate whether MSCs can be used for the treatment of IBD through the induction of Tregs. MSCs were isolated and identified by flow cytometry. The MSCs were transduced with a replication-defective recombinant lentiviral vector carrying GFP in order to be able to trace the injected cells in vivo. Prepared MSCs (1x106) were injected into rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)‑induced colitis via the tail vein; the control rats received phosphate-buffered saline (PBS) alone. Two weeks after the intravenous infusion, the frequency of CD4+CD25+Foxp3 cells in the peripheral blood was examined by flow cytometry. The colon was sectioned and analyzed for histopathological changes. Foxp3 mRNA expression was determined by real-time reverse-transcription polymerase chain reaction (qRT-PCR). In our study, the systemic infusion of MSCs significantly ameliorated the clinical and histopathologic severity of TNBS-induced colitis in contrast to the controls. There was an inverse regulation of mucosal and peripheral Foxp3 expression, suggesting that the MSCs redistributed the Tregs from the mucosa to the blood. Thus, MSCs exhibit immunomodulatory functions and may be used to ameliorate or treat IBD by redistributing regulatory T cells. Therefore, the interactions between transplanted bone marrow-derived MSCs and Tregs should be further investigated; MSCs have tremendous potential for use in the treatment of IBD.