Although it has been preclinically suggested that adipose tissue-derived mesenchymal stem cell (ADSC)-based therapy could effectively treat chronic liver diseases, the hepatic engraftment of ADSCs is still extremely low, which severely limits their long-term efficacy for chronic liver diseases. This study was designed to investigate the impact of antioxidant preconditioning on hepatic engraftment efficiency and therapeutic outcomes of ADSC transplantation in liver fibrotic mice. Liver fibrosis model was established by using intraperitoneal injection of carbon tetrachloride (CCl4) in the male C57BL/6 mice. Subsequently, the ADSCs with or without antioxidant pretreatment (including melatonin and reduced glutathione (GSH)) were administrated into fibrotic mice via tail vein injection. Afterwards, the ADSC transplantation efficiency was analyzed by ex vivo imaging, and the liver functions were assessed by biochemical analysis and histopathological examination, respectively. Additionally, a typical hydrogen peroxide (H2O2)-induced cell injury model was applied to mimic the cell oxidative injury to further investigate the protective effects of antioxidant preconditioning on cell migration, proliferation, and apoptosis of ADSCs. Our data showed that antioxidant preconditioning could enhance the therapeutic effects of ADSCs on liver function recovery by reducing the level of AST, ALT, and TBIL, as well as the content of hepatic hydroxyproline and fibrotic area in liver tissues. Particularly, we also found that antioxidant preconditioning could enhance hepatic engraftment efficiency of ADSCs in liver fibrosis model through inhibiting oxidative injury. Antioxidant preconditioning could effectively improve therapeutic effects of ADSC transplantation for liver fibrosis through enhancing intrahepatic engraftment efficiency by reducing oxidative injuries. These findings might provide a practical strategy for enhancing ADSC transplantation and therapeutic efficiency.

中文翻译：

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通过增强小鼠肝纤维化模型中的肝内植入效率，抗氧化剂预处理可改善脂肪组织来源的间充质干细胞的治疗效果。

尽管临床上已经有人提出基于脂肪组织的间充质干细胞（ADSC）治疗可以有效治疗慢性肝病，但是ADSCs的肝脏植入率仍然非常低，这严重限制了它们对慢性肝病的长期疗效。这项研究旨在调查抗氧化剂预处理对肝纤维化小鼠肝移植效率和ADSC移植治疗效果的影响。通过在雄性C57BL / 6小鼠中腹腔注射四氯化碳（CCl4）建立肝纤维化模型。随后，将经过或未经过抗氧化剂预处理（包括褪黑激素和还原型谷胱甘肽（GSH））的ADSC通过尾静脉注射给药至纤维化小鼠。之后，通过离体成像分析ADSC的移植效率，并分别通过生化分析和组织病理学检查评估肝功能。此外，将典型的过氧化氢（H2O2）诱导的细胞损伤模型用于模拟细胞氧化损伤，以进一步研究抗氧化剂预处理对ADSCs细胞迁移，增殖和凋亡的保护作用。我们的数据表明，抗氧化剂预处理可以通过降低AST，ALT和TBIL的含量以及肝组织中肝羟脯氨酸和纤维化区域的含量来增强ADSC对肝功能恢复的治疗效果。尤其，我们还发现抗氧化剂预处理可以通过抑制氧化损伤来提高ADSCs在肝纤维化模型中的肝移植效率。抗氧化剂预处理可以通过减少氧化损伤来提高肝内移植效率，从而有效改善ADSC移植治疗肝纤维化的疗效。这些发现可能为提高ADSC移植和治疗效率提供实用的策略。