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- W4238723409 abstract "Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers ( Lgr5, Olfm4, and Bmi1 ), enterocyte differentiation markers ( Muc2, Alpi, Chga, and occludin ), and regulatory T (Treg) cells ( Foxp3 ). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines ( IL-1β, TNF-α, IL-6, and MCP-1 ) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research." @default.
- W4238723409 created "2022-05-12" @default.
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- W4238723409 date "2020-12-07" @default.
- W4238723409 modified "2023-10-09" @default.
- W4238723409 title "The therapeutic efficacy of mesenchymal stromal cells on experimental colitis was improved by the IFN-γ and poly(I:C)-priming through promoting the expression of indoleamine 2,3-dioxygenase." @default.
- W4238723409 doi "https://doi.org/10.21203/rs.3.rs-36697/v4" @default.
- W4238723409 hasPublicationYear "2020" @default.
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