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KMID : 1377020190160010051
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Tissue Engineering and Regenerative Medicine
2019 Volume.16 No. 1 p.51 ~ p.58
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Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl4-Induced Liver Fibrosis in Mice
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Kim Yu-Hee
Cho Kyung-Ah
Park Min-Hwa
Kim Han-Su
Park Joo-Won
Woo So-Youn
Ryu Kyung-Ha
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Abstract
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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 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 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.
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.
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KEYWORD
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Tonsil-derived mesenchymal stem cells, Liver fibrosis, Interleukin-1 receptor antagonist
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