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Dexamethasone marginally surpasses MSC-secretomein resolving acute liver failure in mice

Thoria Diab, Eiman M. Adly, Mohamed Hessien

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Molecular Cell Biology Unit, Division of Biochemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt

The anti-inflammatory roles of Mesenchymal stem cells (MSCs) and glucocorticoids are well-reported in both preclinical and clinical studies. However, it is not clear how far MSC-secretome offers sufficient protection against acute liver failure (ALF) compared to glucocorticoids. To answer this query, acute liver failure was induced in mice by a single toxic dose (400 mg/kg) of acetaminophen (APAP). Then mice were treated with Dexamethasone or transfused with MSC-secretome, which was derived from DEX-treated bone marrow mesenchymal stem cells. The results showed that 10 nM DEX has no impact on the viability or the mesenchymal characteristics of MSCs. While the transfusion of MSC-secretome provided a significant therapeutic effect against ALF, it was marginally less effective than DEX treatment. Hepatic markers (ALT, ALP, GGT, and bilirubin) were improved more significantly in DEX-treated mice than in MSC-secretome treated group. This improvement was accompanied by marked relief in the oxidative assessed in the liver as Nrf-2, MDA, and GSH. Additionally, the normal levels of angiogenic (VEGF), and inflammatory (TNF-α) markers were effectively restored after DEX treatment. Also, both MSC-secretome and DEX resolved liver necrosis. In summary, these data suggest that dexamethasone demonstrates a better therapeutic effect than MSC-secretome in the treatment of ALF. Further studies are necessary to standardize MSC-secretome as an acellular therapeutic approach. 

Key words: BM-MSCs, dexamethasone, acute liver failure, hepatoma cells, paracetamol, inflammation