Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms24098092
Keywords
mesenchymal stem; stromal cells (MSCs); small extracellular vesicles (sEVs); fibrosis; non-alcoholic steatohepatitis (NASH); immunomodulation; M2 macrophage
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Mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) have shown promise in treating various human diseases in animal models. However, the potential for contraindication in fibrotic diseases due to their ability to induce pro-fibrotic M2 macrophage polarization is an important consideration. Despite this, MSC-sEVs were found to be effective in reducing liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH).
Mesenchymal stem/stromal cell small extracellular vesicles (MSC-sEVs) have shown promise in treating a wide range of animal models of various human diseases, which has led to their consideration for clinical translation. However, the possibility of contraindication for MSC-sEV use is an important consideration. One concern is that MSC-sEVs have been shown to induce M2 macrophage polarization, which is known to be pro-fibrotic, potentially indicating contraindication in fibrotic diseases such as liver fibrosis. Despite this concern, previous studies have shown that MSC-sEVs alleviate high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH). To assess whether the pro-fibrotic M2 macrophage polarization induced by MSC-sEVs could worsen liver fibrosis, we first verified that our MSC-sEV preparations could promote M2 polarization in vitro prior to their administration in a mouse model of NASH. Our results showed that treatment with MSC-sEVs reduced or had comparable NAFLD Activity Scores and liver fibrosis compared to vehicle- and Telmisartan-treated animals, respectively. Although CD163(+) M2 macrophages were increased in the liver, and serum IL-6 levels were reduced in MSC-sEV treated animals, our data suggests that MSC-sEV treatment was efficacious in reducing liver fibrosis in a mouse model of NASH despite an increase in pro-fibrotic M2 macrophage polarization.
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