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  • Title: Bone marrow-derived mesenchymal stem cells favor the immunosuppressive T cells skewing in a Helicobacter pylori model of gastric cancer.
    Author: Lin R, Ma H, Ding Z, Shi W, Qian W, Song J, Hou X.
    Journal: Stem Cells Dev; 2013 Nov 01; 22(21):2836-48. PubMed ID: 23777268.
    Abstract:
    Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in Helicobacter pylori-induced gastric carcinogenesis. While the mechanism is not well understood, BM-MSCs have been shown to contribute to the immunosuppressive response found in a number of diseases. Here, BM-MSCs were transplanted into the stomach of mice with a 44-week mouse-adapted H. pylori infection. At day 28 post-transplantation, BM-MSCs migrated from the subserosal to the mucosal layer of the stomach. The grafted BM-MSCs significantly stimulated systemic and local interleukin-10 (IL-10)-secreting T cell and regulatory T cell (Treg) functions. This observation was correlated with an increased percentage of CD4⁺IL-10⁺ cells and CD4⁺CD25⁺FoxP3⁺ cells in splenic mononuclear cells compared with H. pylori-infected mice not receiving BM-MSCs. Moreover, inhibitory cytokines IL-10 and transforming growth factor-β1 increased in the gastric tissue, while there was a decrease in inflammatory interferon-γ (IFN-γ). BM-MSC-transplanted mice also developed elevated IL-10/IFN-γ secreting and Treg/Th17 ratios. A coculture system in the presence or absence of BM-MSCs was also established to evaluate the immune responses in vitro. An increase in IL-10-secreting T cells and Tregs, associated with increased expression of Gata-3 and FoxP3, generation of IL-10 in the supernatant, and proliferation of gastric epithelial cells (GECs) was observed. These findings demonstrate that transplantation of BM-MSCs into a chronic H. pylori-infected mouse model results in the generation of an immunosuppressive environment. The local and systemic immunosuppression mediated by BM-MSCs likely contributed to an environment that is compatible with the development of H. pylori-induced gastric cancer.
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