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ABSTRACT: Background
Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear.Methods
MSCs were isolated from the bone marrow (BM) of 4-6-week-old male C57BL/6?N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10?days. The mice were given intraperitoneal injections of MSCs with or without transfection or AG490, recombinant mouse tumor necrosis factor (TNF)-?-stimulated gene/protein 6 (rmTSG-6), or saline at day 10. Blood samples and hepatic tissues were collected at day 11. Various assays such as biochemistry, histology, and flow cytometry were performed.Results
MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-?, but increasing glutathione, IL-10, and TSG-6, compared to control mice. Few MSCs engrafted into the inflamed liver. Knockdown of TSG-6 in MSCs significantly attenuated their effects, and injection of rmTSG-6 achieved similar effects to MSCs. The signal transducer and activator of transcription 3 (STAT3) was activated in mice with AH, and MSCs and rmTSG-6 inhibited the STAT3 activation. Injection of MSCs plus AG490 obtained more alleviation of liver injury than MSCs alone.Conclusions
BM-MSCs injected into mice with AH do not engraft the liver, but they secrete TSG-6 to reduce liver injury and to inhibit STAT3 activation.
SUBMITTER: Wan YM
PROVIDER: S-EPMC6958598 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Wan Yue-Meng YM Li Zhi-Qiang ZQ Zhou Qiong Q Liu Chang C Wang Men-Jie MJ Wu Hui-Xin HX Mu Yun-Zhen YZ He Yue-Feng YF Zhang Yuan Y Wu Xi-Nan XN Li Yu-Hua YH Xu Zhi-Yuan ZY Wu Hua-Mei HM Xu Ying Y Yang Jin-Hui JH Wang Xiao-Fang XF
Stem cell research & therapy 20200113 1
<h4>Background</h4>Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear.<h4>Methods</h4>MSCs were isolated from the bone marrow (BM) of 4-6-week-old male C57BL/6 N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. The mice were given intraperitoneal injections of MSCs with or without tra ...[more]