期刊
CYTOTHERAPY
卷 18, 期 5, 页码 630-641出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2016.02.002
关键词
cell therapy; dextran sulfate sodium-induced colitis; immunosuppression; inflammatory bowel disease; toll-like receptors; umbilical cord-derived mesenchymal stromal cells
类别
资金
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (Fondecyt), Santiago Chile [1130444]
Background aims. Immunomodulatory properties of human umbilical cord derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty of this study is that although modulation of human MSCs activity by TLRs is not a new concept, this is the first time that short TLR pre-conditioning has been carried out in a murine inflammatory model of acute colitis. Methods. C57BL/6 mice were exposed to 2.5% dextran sulfate sodium (DSS) in drinking water ad libitum for 7 days. At days 1 and 3, mice were injected intraperitoneally with 1 x 10(6) UCMSCs untreated or TLR3 and TLR4 pre-conditioned UCMSCs. UCMSCs were preconditioned with poly(I:C) for TLR3 and LPS for TLR4 for 1 h at 37 degrees C and 5% CO2. We evaluated clinical signs of disease and body weights daily. At the end of the experiment, colon length and histological changes were assessed. Results. poly(I:C) pre-conditioned UCMSCs significantly ameliorated the clinical and histopathological severity of DSS-induced colitis compared with UCMSCs or LPS pre-conditioned UCMSCs. In contrast, infusion of LPS pre-conditioned UCMSCs significantly increased clinical signs of disease, colon shortening and histological disease index in DSS-induced colitis. Conclusions. These results show that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs, which is a major breakthrough for developing improved treatments to patients with inflammatory bowel disease.
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