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Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

Published on Jun 1, 2019in Research in Veterinary Science 1.75
· DOI :10.1016/j.rvsc.2019.06.012
Woo-Jin Song4
Estimated H-index: 4
(SNU: Seoul National University),
Qiang Li4
Estimated H-index: 4
(SNU: Seoul National University)
+ 5 AuthorsHwa-Young Youn13
Estimated H-index: 13
(SNU: Seoul National University)
Cite
Abstract
Abstract Canine inflammatory bowel disease (IBD) is an intractable autoimmune disorder that results in various gastrointestinal and systemic symptoms. Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. Furthermore, although it is known that MSCs pre-treated with pro-inflammatory cytokines show enhanced anti-inflammatory properties via the secretion of soluble factors, the underlying mechanisms of IBD remain unclear. The aim of this study was to demonstrate the therapeutic effects and corresponding mechanisms of canine adipose tissue-derived (cAT)-MSCs stimulated with TNF-α in mouse models of IBD. Mice with dextran sulfate sodium (DSS)- or dinitrobenzene sulfonic acid (DNBS)-induced colitis were injected intraperitoneally with cAT-MSCs pre-treated with TNF-α. Colitis severity was assessed and colon tissues were collected for histopathological, enzyme-linked immunosorbent assay, and flow cytometry analysis. cAT-MSCs stimulated with TNF-α secreted higher concentrations of immunomodulatory factors such as TSG-6 and PGE2, which play a key role in inducing phenotypic alterations in macrophages. Consequently, TNF-α-pre-treated cAT-MSCs further regulated colonic inflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-10, and ameliorated DSS- or DNBS-induced colitis in mice. Additionally, we demonstrated that M1 macrophages (F4/80 + /iNOS + cells) were decreased in colon tissues from mice treated with TNF-α-pre-treated cAT-MSCs, whereas M2 macrophages (F4/80 + /CD206 + cells) were increased. These results may suggest a new cell-based therapeutic option for treating IBD.
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References43
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Published on Dec 1, 2018in Stem Cell Research & Therapy 4.63
Woo-Jin Song4
Estimated H-index: 4
(SNU: Seoul National University),
Qiang Li4
Estimated H-index: 4
(SNU: Seoul National University)
+ 4 AuthorsHwa-Young Youn13
Estimated H-index: 13
(SNU: Seoul National University)
Background Inflammatory bowel disease (IBD) is an intractable autoimmune disorder that markedly deteriorates one’s 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 mechani...
Published on Aug 1, 2018in Research in Veterinary Science 1.75
Hye-Mi Yang1
Estimated H-index: 1
(SNU: Seoul National University),
Woo-Jin Song4
Estimated H-index: 4
(SNU: Seoul National University)
+ 5 AuthorsHwa-Young Youn13
Estimated H-index: 13
(SNU: Seoul National University)
Abstract Mesenchymal stem cells (MSCs) have been used in studies on treatment of various diseases, and their application to immune-mediated diseases has garnered interest. Various methods for enhancing the immunomodulation effect of human MSCs have been used; however, similar approaches for canine MSCs are relatively unexplored. Accordingly, we evaluated immunomodulatory effects and mechanisms in canine MSCs treated with TNF-α and IFN-γ. Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were i...
Published on Dec 1, 2017in Scientific Reports 4.01
Woo-Jin Song4
Estimated H-index: 4
(SNU: Seoul National University),
Qiang Li4
Estimated H-index: 4
(SNU: Seoul National University)
+ 4 AuthorsHwa-Young Youn13
Estimated H-index: 13
(SNU: Seoul National University)
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-MS...
Published on Dec 1, 2017in Scientific Reports 4.01
Ji-young Song7
Estimated H-index: 7
(UOU: University of Ulsan),
Hyo Jeong Kang10
Estimated H-index: 10
(UOU: University of Ulsan)
+ 4 AuthorsJene Choi17
Estimated H-index: 17
(UOU: University of Ulsan)
Human umbilical cord mesenchymal stem cells (hUC-MSCs), originating in Wharton’s jelly, are multipotent stem cells that home to damaged tissues and can modulate the immune system. We examined whether administering extracts of MSCs (MSC-Ex) instead of MSCs could augment the beneficial effects of MSC therapy by overcoming the low homing efficiency of MSCs systemically administered in inflammatory bowel diseases (IBD). Dextran sodium sulfate-induced colitis model was established in C57BL/6 mice, an...
Published on Sep 1, 2017in Veterinary Immunology and Immunopathology 1.85
Hyung-Kyu Chae2
Estimated H-index: 2
(SNU: Seoul National University),
Woo-Jin Song4
Estimated H-index: 4
(SNU: Seoul National University)
+ 5 AuthorsHwa-Young Youn13
Estimated H-index: 13
(SNU: Seoul National University)
Abstract Mesenchymal stem cells (MSCs) have immunomodulatory functions and differentiation capacity, and their clinical use is increasing in veterinary species. Although MSCs have been applied in the treatment in various inflammatory diseases, mechanistic research on feline MSCs is lacking. Accordingly, in this study, we aimed to investigate the immunomodulatory mechanisms of MSCs isolated from feline adipose tissue (fATMSCs). fATMSCs from healthy cats were cultured in an appropriate manner and ...
Published on Jun 6, 2017in Oncotarget
Fei Mao1
Estimated H-index: 1
(Jiangsu University),
Qiang Tu1
Estimated H-index: 1
+ 4 AuthorsWenrong Xu33
Estimated H-index: 33
(Jiangsu University)
// Fei Mao 1,* , Qiang Tu 2,* , Li Wang 1 , Fuliang Chu 3 , Xia Li 4 , Haiyan S. Li 5 and Wenrong Xu 1 1 Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China 2 Jiangning Hospital of Nanjing, Nanjing, Jiangsu, P.R. China 3 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 Department of Gastroenterology, Binzhou Medical University Yantai Affili...
Published on Jan 1, 2017in Stem Cells 5.61
Hyung Sik Kim45
Estimated H-index: 45
(PNU: Pusan National University),
Ji Hyun Lee1
Estimated H-index: 1
(St Mary's Hospital)
+ 3 AuthorsTae-Yoon Kim24
Estimated H-index: 24
(St Mary's Hospital)
Abstract Mesenchymal stem cells (MSCs) have been proven to be therapeutically effective against atopic dermatitis (AD) in preclinical studies. However, the safety and efficacy of MSCs against AD have not yet been investigated in a clinical study. To establish the safety and efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) in AD, thirty-four adult patients with moderate-to-severe AD were enrolled in two phase trials with a follow-up for 1 month and 3 months, respectively. Patients ...
Published on Dec 1, 2016in Stem Cell Research & Therapy 4.63
Nikolay Bazhanov9
Estimated H-index: 9
(Texas A&M Health Science Center College of Medicine),
Joni Ylostalo21
Estimated H-index: 21
(Texas A&M Health Science Center College of Medicine)
+ 4 AuthorsDarwin J. Prockop118
Estimated H-index: 118
(Texas A&M Health Science Center College of Medicine)
Background Mesenchymal stem/progenitor cells (MSC) have shown beneficial effects in many models of disease in part by modulating excessive inflammatory and immune responses. Frequently the beneficial effects of MSC persist long after their disappearance from host tissues, suggesting that MSC interact with intermediate cells in the host that relay or amplify their effects. The cells have usually been injected intravenously, but beneficial effects have also been reported with intraperitoneal (IP) ...
Published on Dec 1, 2016in Cell Death and Disease 5.96
Tae-Hoon Shin10
Estimated H-index: 10
,
Hyung Sik Kim45
Estimated H-index: 45
+ 10 AuthorsSeung Hee Lee34
Estimated H-index: 34
Human umbilical cord blood-stem cells direct macrophage polarization and block inflammasome activation to alleviate rheumatoid arthritis
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