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Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro
DC Field | Value | Language |
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dc.contributor.author | 김우람 | - |
dc.date.accessioned | 2024-07-18T05:26:32Z | - |
dc.date.available | 2024-07-18T05:26:32Z | - |
dc.date.issued | 2024-03 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/200093 | - |
dc.description.abstract | Background: A significant unmet need in inflammatory bowel disease is the lack of anti-fibrotic agents targeting intestinal fibrosis. This study aimed to investigate the anti-fibrogenic properties and mechanisms of the conditioned medium (CM) from human umbilical cord/placenta-derived mesenchymal stem cells (UC/PL-MSC-CM) in a murine intestinal fibrosis model and human primary intestinal myofibroblasts (HIMFs). Methods: UC/PL-MSC-CM was concentrated 15-fold using a 3 kDa cut-off filter. C57BL/6 mice aged 7 weeks old were randomly assigned to one of four groups: (1) control, (2) dextran sulfate sodium (DSS), (3) DSS + CM (late-phase treatment), and (4) DSS + CM (early-phase treatment). Chronic DSS colitis and intestinal fibrosis was induced by three cycles of DSS administration. One DSS cycle consisted of 7 days of oral DSS administration (1.75%, 2%, and 2.5% DSS), followed by 14 days of drinking water. UC/PL-MSC-CM was intraperitoneally administered in the late phase (from day 50, 10 times) or early phase (from day 29, 10 times) of DSS cycles. HIMFs were treated with TGF-β1 and co-treated with UC/PL-MSC-CM (10% of culture media) in the cellular model. Results: In the animal study, UC/PL-MSC-CM reduced submucosa/muscularis propria thickness and collagen deposition, which improved intestinal fibrosis in chronic DSS colitis. The UC/PL-MSC-CM significantly reduced the expressions of procollagen1A1 and α-smooth muscle actin, which DSS significantly elevated. The anti-fibrogenic effect was more apparent in the UC-MSC-CM or early-phase treatment model. The UC/PL-MSC-CM reduced procollagen1A1, fibronectin, and α-smooth muscle actin expression in HIMFs in the cellular model. The UC/PL-MSC-CM downregulated fibrogenesis by suppressing RhoA, MRTF-A, and SRF expression. Conclusions: Human UC/PL-MSC-CM inhibits TGF-β1-induced fibrogenic activation in HIMFs by blocking the Rho/MRTF/SRF pathway and chronic DSS colitis-induced intestinal fibrosis. Thus, it may be regarded as a novel candidate for stem cell-based therapy of intestinal fibrosis. © The Author(s) 2024. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | BioMed Central | - |
dc.relation.isPartOf | STEM CELL RESEARCH & THERAPY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Actins / metabolism | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Colitis* / chemically induced | - |
dc.subject.MESH | Colitis* / metabolism | - |
dc.subject.MESH | Colitis* / therapy | - |
dc.subject.MESH | Culture Media, Conditioned / metabolism | - |
dc.subject.MESH | Culture Media, Conditioned / pharmacology | - |
dc.subject.MESH | Dextran Sulfate / toxicity | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Fibrosis | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunologic Factors | - |
dc.subject.MESH | Mesenchymal Stem Cells* / metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Transforming Growth Factor beta1 / metabolism | - |
dc.subject.MESH | Umbilical Cord | - |
dc.title | Human umbilical cord/placenta mesenchymal stem cell conditioned medium attenuates intestinal fibrosis in vivo and in vitro | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학교실) | - |
dc.contributor.googleauthor | Yoon Jeong Choi | - |
dc.contributor.googleauthor | Woo Ram Kim | - |
dc.contributor.googleauthor | Duk Hwan Kim | - |
dc.contributor.googleauthor | Jee Hyun Kim | - |
dc.contributor.googleauthor | Jun Hwan Yoo | - |
dc.identifier.doi | 10.1186/s13287-024-03678-4 | - |
dc.contributor.localId | A00758 | - |
dc.relation.journalcode | J02681 | - |
dc.identifier.eissn | 1757-6512 | - |
dc.identifier.pmid | 38454492 | - |
dc.subject.keyword | Conditioned medium | - |
dc.subject.keyword | Intestinal fibrosis | - |
dc.subject.keyword | Mesenchymal stem cells | - |
dc.subject.keyword | Placenta | - |
dc.subject.keyword | Umbilical cord | - |
dc.contributor.alternativeName | Kim, Woo Ram | - |
dc.contributor.affiliatedAuthor | 김우람 | - |
dc.citation.volume | 15 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 69 | - |
dc.identifier.bibliographicCitation | STEM CELL RESEARCH & THERAPY, Vol.15(1) : 69, 2024-03 | - |
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