Gastroenterology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming City, 650101, Yunnan Province, China.
Public Health Institute of Kunming Medical University, Kunming City, 650500, Yunnan Province, China.
Stem Cell Res Ther. 2020 Jan 13;11(1):24. doi: 10.1186/s13287-019-1547-8.
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.
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)-α-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.
MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-ɑ, 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.
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.
间充质干细胞（MSCs）是一种多能细胞，可用于治疗肝脏疾病。然而，MSCs 治疗酒精性肝炎（AH）的疗效及其潜在机制尚不清楚。
从 4-6 周龄雄性 C57BL/6N 小鼠的骨髓（BM）中分离 MSCs。通过慢性 binge 乙醇喂养 10 天在雌性小鼠中诱导 AH。第 10 天，用 MSC 或 MSC 转染或 AG490、重组鼠肿瘤坏死因子（TNF）-α刺激基因/蛋白 6（rmTSG-6）或生理盐水对小鼠进行腹腔内注射。第 11 天采集血液样本和肝组织。进行了各种测定，如生化、组织学和流式细胞术。
与对照组相比，MSC 减少了小鼠的 AH，降低了肝/体重比、肝损伤、血液和肝脂质、丙二醛、白细胞介素（IL）-6 和 TNF-α，而增加了谷胱甘肽、IL-10 和 TSG-6。很少有 MSC 植入到发炎的肝脏中。在 MSC 中转录沉默 TSG-6 可显著减弱其作用，而注射 rmTSG-6 可达到与 MSC 相似的效果。在患有 AH 的小鼠中，信号转导和转录激活因子 3（STAT3）被激活，MSC 和 rmTSG-6 抑制了 STAT3 的激活。与单独注射 MSC 相比，注射 MSC 加 AG490 可获得更多的肝损伤缓解。
注射到 AH 小鼠肝脏中的 BM-MSCs 不会植入肝脏，但它们分泌 TSG-6 以减轻肝损伤并抑制 STAT3 激活。
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