Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl4-Induced Liver Fibrosis in Mice
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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.
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.
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.
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.
KeywordsTonsil-derived mesenchymal stem cells Liver fibrosis Interleukin-1 receptor antagonist
This work was supported by the National Research Foundation (NRF) of Korea, funded by the Ministry of Science and ICT (2017R1E1A1A01073021) and Intramural Research Promotion Grants from Ewha Womans University School of Medicine.
Compliance with ethical standards
Conflicts of interest
The authors declare no actual or potential conflict of interest.
All experimental procedures and protocols were approved by the Animal Ethics Committee at Ewha Womans University College of Medicine (Seoul, Korea; No. ESM 18-0405), and experiments were performed in accordance with relevant guidelines and regulations.
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