TSG-6 Secreted by Human Adipose Tissue-derived Mesenchymal Stem Cells Ameliorates DSS-induced colitis by Inducing M2 Macrophage Polarization in Mice

• Published in: Scientific reports Vol. 7; no. 1; pp. 5187 - 14
• Main Authors: Song, Woo-Jin, Li, Qiang, Ryu, Min-Ok, Ahn, Jin-Ok, Ha Bhang, Dong, Chan Jung, Yun, Youn, Hwa-Young
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.07.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/21; 13/51; 13/89; 38/77; 631/250/2504/342; 631/250/38; 631/532/2074; 64/60; 82/80; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - metabolism; Animals; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell culture; Colitis; Colitis - etiology; Colitis - metabolism; Colitis - pathology; Colon; Cytokines; Dextran; Dextran sulfate; Dextran Sulfate - adverse effects; Disease Models, Animal; Gene Knockdown Techniques; Humanities and Social Sciences; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - etiology; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Intestine; Macrophage Activation - immunology; Macrophages; Macrophages - immunology; Macrophages - metabolism; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; Mice; multidisciplinary; Rodents; Science; Science (multidisciplinary); siRNA; Sodium; Stem cell transplantation; Stem cells; Sulfates; Tumor necrosis factor; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-04766-7

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 human adipose tissue-derived (hAT)-MSCs in an IBD mouse model and to explore the mechanisms of the regulation of inflammation. Dextran sulfate sodium-induced colitis mice were infused with hAT-MSCs intraperitoneally and colon tissues were collected on day 10. hAT-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 hAT-MSCs, 0.001% of all intraperitoneally injected hAT-MSCs, were detected in the inflamed colon. To investigate the effects of hAT-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 hAT-MSCs induces M2 macrophages. In vivo , hAT-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, hAT-MSC-produced TSG-6 can ameliorate IBD by inducing M2 macrophage switch in mice.