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

• Published in: Stem cell research & therapy 2021-01, Vol.12 (1), p.37-37, Article 37
• Main Authors: Lim, Ji-Young, Kim, Byung-Su, Ryu, Da-Bin, Kim, Tae Woo, Park, Gyeongsin, Min, Chang-Ki
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Binding sites; Body weight; Body weight loss; Cell proliferation; Colitis; Colon; Cytokines; Dextran; Dextran sulfate sodium-induced colitis; Drinking water; Enterocytes; Experiments; Foxp3 protein; Gene expression; IL-1β; Indoleamine 2,3-dioxygen; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 6; Ligands; Lymphocytes; Lymphocytes T; Mesenchymal stem cells; Mesenchymal stromal cells; Mesenchyme; Monocyte chemoattractant protein 1; Paneth cells; Polyinosinic:polycytidylic acid; Proteins; Small intestine; Sodium sulfate; Stromal cells; Toll-like receptors; Tryptophan 2,3-dioxygenase; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-020-02087-7

Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) 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. 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. 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 upregulation in colon tissue and diminished the protective effects of the primed MSC. 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.