Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CCl4-Induced Liver Fibrosis in Mice.

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 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.

• Authors: Yu-Hee Kim, Kyung-Ah Cho, Minhwa Park, Han Su Kim, Joo-Won Park, So-Youn Woo, Kyung-Ha Ryu
• Journal: Tissue engineering and regenerative medicine (Tissue Eng Regen Med) Vol. 16 Issue 1 Pg. 51-58 (Feb 2019) ISSN: 2212-5469 [Electronic] Korea (South)
• PMID: 30815350 (Publication Type: Journal Article)