Tissue Eng Regen Med.  2019 Feb;16(1):51-58. 10.1007/s13770-018-0160-8.

Conditioned Medium from Tonsil-Derived Mesenchymal Stem Cells Relieves CClâ‚„-Induced Liver Fibrosis in Mice

• Kim YH
• Cho KA
• Park M
• Kim HS
• Park JW
• Woo SY
• Ryu KH

• KMID: 2441255
• DOI: http://doi.org/10.1007/s13770-018-0160-8

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 (CClâ‚„) 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 CClâ‚„-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 CClâ‚„ 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.

Keyword

Tonsil-derived mesenchymal stem cells; Liver fibrosis; Interleukin-1 receptor antagonist

MeSH Terms

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
Carbon Tetrachloride
Collagen Type I
Culture Media, Conditioned
Interleukin 1 Receptor Antagonist Protein
Metalloproteases
Transforming Growth Factor beta