Mesenchymal stem cells recruit macrophages to alleviate experimental colitis through TGFβ1.

Abstract

BACKGROUND/AIMS: Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate dextran sulfate sodium (DSS) -induced colitis through modulation of transforming growth factor β (TGFβ) receptor signaling. However, the exact molecular mechanisms are not known. METHODS: Here, we transplanted primary mouse MSCs or injected TGFβ1 into mice with DSS-induced colitis. Cells were purified by flow cytometry. Gene expression was analyzed by RT-qPCR. RESULTS: We found that MSCs significantly alleviated the DSS-induced colitis, and the major sources for TGFβ1 were macrophages that were recruited by MSCs. Specific ablation of macrophages completely abolished the anti-inflammatory effects of MSCs. On the other hand, TGFβ1 administration, without the presence of MSCs, was sufficient to reduce the severity of DSS-induced colitis. CONCLUSIONS: Taken together, our data suggest that MSCs transplantation may recruit macrophages to produce TGFβ1, which mitigates the pathology of colitis. Thus, MSCs transplantation appears to be a promising therapy for severe enteritis.