Previous studies have revealed that mesenchymal stem cells (MSCs) alleviate inflammatory bowel disease (IBD) by modulating inflammatory cytokines in the inflamed intestine. However, the mechanisms underlying these effects are not completely understood. We sought to investigate the therapeutic effects of canine adipose tissue-derived (cAT)-MSCs in an inflammatory bowel disease mouse model and to explore the mechanisms of the regulation of inflammation.
Dextran sulfate sodium-induced colitis mice were infused with cAT-MSCs intraperitoneally and colon tissues were collected on day 10. Data were compared by one-way ANOVA using the GraphPad Prism v.6.01 software.
cAT-MSCs were shown to induce the expression of M2 macrophage markers and to regulate the expression of pro- and anti-inflammatory cytokines in the colon. Quantitative real time-PCR analyses demonstrated that less than 20 cAT-MSCs, 0.001% of all intraperitoneally injected cAT-MSCs, were detected in the inflamed colon. To investigate the effects of cAT-MSC-secreted factors in vitro, transwell co-culture system was used, demonstrating that tumour necrosis factor-α-induced gene/protein 6 (TSG-6) released by cAT-MSCs induces M2 macrophages. In vivo, cAT-MSCs transfected with TSG-6 small interfering RNA, administered intraperitoneally, were not able to induce M2 macrophage phenotype switch in the inflamed colon and had no significant effects on IBD severity.
In conclusion, cAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage switch in mice.
DVM, Ph.D. candidate
Seoul National University
Thursday, June 14
10:45 AM – 11:00 AM
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