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.
Bibliographical noteFunding Information:
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.
Acknowledgements 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.
© 2018, The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature.
- Interleukin-1 receptor antagonist
- Liver fibrosis
- Tonsil-derived mesenchymal stem cells