Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl₄-Induced Liver Fibrosis in Mice
10.1007/s13770-018-0160-8
- Author:
Yu Hee KIM
1
;
Kyung Ah CHO
;
Minhwa PARK
;
Han Su KIM
;
Joo Won PARK
;
So Youn WOO
;
Kyung Ha RYU
Author Information
1. Department of Microbiology, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea.
- Publication Type:Original Article
- Keywords:
Tonsil-derived mesenchymal stem cells;
Liver fibrosis;
Interleukin-1 receptor antagonist
- MeSH:
Animals;
Carbon Tetrachloride;
Collagen Type I;
Culture Media, Conditioned;
Fibrosis;
Humans;
Inflammation;
Interleukin 1 Receptor Antagonist Protein;
Liver Cirrhosis;
Liver Failure;
Liver;
Mesenchymal Stromal Cells;
Metalloproteases;
Mice;
Mortality;
Myoblasts;
Transforming Growth Factor beta
- From:
Tissue Engineering and Regenerative Medicine
2019;16(1):51-58
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 (CCl₄) and investigated the therapeutic potential of conditionedmedium from tonsil-derivedMSCs (T-MSCCM). 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 CCl₄-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 CCl₄ injection, whereas treatment with T-MSC CM or IL-1Ra downregulated their expression. CONCLUSION: 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.