Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl 4 -Induced Liver Fibrosis in Mice
- 주제(키워드) Interleukin-1 receptor antagonist , Liver fibrosis , Tonsil-derived mesenchymal stem cells
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published
- 발행기관 Korean Tissue Engineering and Regenerative Medicine Society
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000159970
- 본문언어 영어
- Published As http://dx.doi.org/10.1007/s13770-018-0160-8
- PubMed https://pubmed.ncbi.nlm.nih.gov/30815350
초록/요약
Background:: The liver is an organ with remarkable regenerative capacity; however, once chronic fibrosis occurs, liver failure follows, with high mortality and morbidity rates. Continuous exposure to proinflammatory stimuli exaggerates the pathological process of liver failure; therefore, immune modulation is a potential strategy to treat liver fibrosis. Mesenchymal stem cells (MSCs) with tissue regenerative and immunomodulatory potential may support the development of therapeutics for liver fibrosis. Methods:: Here, we induced hepatic injury in mice by injecting carbon tetrachloride (CCl 4 ) and investigated the therapeutic potential of conditioned medium from tonsil-derived MSCs (T-MSC CM). In parallel, we used recombinant human IL-1Ra, which, as we have previously shown, is secreted exclusively from T-MSCs and resolves the fibrogenic activation of myoblasts. Hepatic inflammation and fibrosis were determined by histological analyses using H&E and Picro-Sirius Red staining. Results:: The results demonstrated that T-MSC CM treatment significantly reduced inflammation as well as fibrosis in the CCl 4 -injured mouse liver. IL-1Ra injection showed effects similar to T-MSC CM treatment, suggesting that T-MSC CM may exert anti-inflammatory and anti-fibrotic effects via the endogenous production of IL-1Ra. The expression of genes involved in fibrosis was evaluated, and the results showed significant induction of alpha-1 type I collagen, transforming growth factor beta, and tissue inhibitor of metalloproteases 1 upon CCl 4 injection, whereas treatment with T-MSC CM or IL-1Ra downregulated their expression. Conclusions:: Taken together, these data support the therapeutic potential of T-MSC CM and/or IL-1Ra for the alleviation of liver fibrosis, as well as in treating diseases involving organ fibrosis. © 2018, The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature.
more