The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People's Republic of China.
Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350007, People's Republic of China.
Stem Cell Res Ther. 2020 Jun 16;11(1):237. doi: 10.1186/s13287-020-01763-y.
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 (CCl) 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 (HO)-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.
虽然已有临床前研究表明脂肪组织来源的间充质干细胞（ADSC）疗法可有效治疗慢性肝病，但 ADSC 的肝内定植率仍极低，这严重限制了其对慢性肝病的长期疗效。本研究旨在探讨抗氧化预处理对肝纤维化小鼠 ADSC 移植肝内定植效率和治疗效果的影响。
雄性 C57BL/6 小鼠腹腔注射四氯化碳（CCl）建立肝纤维化模型。随后，通过尾静脉注射将未经抗氧化预处理（包括褪黑素和还原型谷胱甘肽（GSH））和经抗氧化预处理的 ADSC 注入纤维化小鼠体内。然后，通过离体成像分析 ADSC 移植效率，通过生化分析和组织病理学检查分别评估肝功能。此外，应用典型的过氧化氢（HO）诱导的细胞损伤模型模拟细胞氧化损伤，进一步研究抗氧化预处理对 ADSC 迁移、增殖和凋亡的保护作用。
我们的数据表明，抗氧化预处理通过降低 AST、ALT 和 TBIL 水平以及肝组织中羟脯氨酸含量和纤维化面积，可增强 ADSC 对肝功能恢复的治疗作用。特别是，我们还发现抗氧化预处理可以通过抑制氧化损伤来提高 ADSC 在肝纤维化模型中的肝内定植效率。
抗氧化预处理可通过减少氧化损伤有效提高 ADSC 移植治疗肝纤维化的疗效，从而提高 ADSC 的肝内定植效率。这些发现可能为提高 ADSC 移植和治疗效率提供了一种实用策略。
