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TSG-6 released from intraperitoneally injected canine adipose tissue-derived mesenchymal stem cells ameliorate inflammatory bowel disease by inducing M2 macrophage switch in mice

Cited 40 time in Web of Science Cited 45 time in Scopus
Authors
Song, Woo-Jin; Li, Qiang; Ryu, Min-Ok; Ahn, Jin-Ok; Bhang, Dong Ha; Jung, Yun Chan; Youn, Hwa-Young
Issue Date
2018-04-06
Publisher
BioMed Central
Citation
Stem Cell Research & Therapy, 9(1):91
Keywords
TSG-6Mesenchymal stem cellsInflammatory bowel diseaseCanineCell therapyImmunomodulationM2 macrophage
Abstract
Background
Inflammatory bowel disease (IBD) is an intractable autoimmune disorder that markedly deteriorates ones quality of life. Mesenchymal stem cells (MSCs) alleviate inflammation by modulating inflammatory cytokines in inflamed tissues, and have been suggested as a promising alternative for IBD treatment in human and veterinary cases. Furthermore, tumor necrosis factor-α-induced gene/protein 6 (TSG-6) is a key factor influencing MSC immunomodulatory properties; however, the precise mechanism of TSG-6 release from canine MSCs in IBD remains unclear. This study aimed to assess the therapeutic effects of canine adipose tissue-derived (cAT)-MSC-produced TSG-6 in an IBD mouse model and to explore the mechanisms underlying the immunomodulatory properties.

Methods
Mice with dextran sulfate sodium-induced colitis were administered cAT-MSCs intraperitoneally; colon tissues were collected on day 10 for histopathological, quantitative real-time polymerase chain reaction, and immunofluorescence analyses.

Results
cAT-MSC-secreted TSG-6 ameliorated IBD and regulated colonic expression of pro- and anti-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-10. To investigate the effect of cAT-MSC-secreted TSG-6 on activated macrophages in vitro, a transwell coculture system was used; TSG-6 released by cAT-MSCs induced a macrophage phenotypic switch from M1 to M2. The cAT-MSC-secreted TSG-6 increased M2 macrophages in the inflamed colon in vivo.

Conclusions
TSG-6 released from cAT-MSCs can alleviate dextran sulfate sodium-induced colitis by inducing a macrophage phenotypic switch to M2 in mice.
ISSN
1757-6512
Language
English
URI
https://hdl.handle.net/10371/141235
DOI
https://doi.org/10.1186/s13287-018-0841-1
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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