Hepatology Department, First Hospital of Jilin University, No. 1, Xinmin Street, Changchun, 130000, Jilin, People's Republic of China.
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, 2555 JingYue Street, Changchun, 130000, Jilin, People's Republic of China.
Stem Cell Res Ther. 2022 Nov 12;13(1):517. doi: 10.1186/s13287-022-03201-7.
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are increasingly being studied in clinical trials of end-stage liver disease because of their good tissue repair and anti-inflammatory effects. hUC-MSC exosomes are vesicles with spherical structures secreted by cells that produce them. The diameter of exosomes is much smaller than that of hUC-MSCs, suggesting that exosomes might be a novel and safer therapeutic product of mesenchymal stem cells. As exosomes have been suggested to have biochemical functions similar to those of hUC-MSCs, this study investigated the efficiency of hUC-MSC-derived exosomes in protecting against nonalcoholic steatohepatitis using an MCD-induced mouse model.
Human umbilical cord mesenchymal stem cell-derived exosomes were extracted and purified. The effect of these exosomes on disease progression in an MCD-induced nonalcoholic steatohepatitis mouse model was investigated.
The results showed that UC-MSC exosomes intravenously transplanted into mice with MCD-induced NASH improved MCD-induced body weight loss and liver damage in a mouse model. Additionally, the inflammatory cytokines in liver tissue were reduced, which may be caused by exosome-induced macrophage anti-inflammatory phenotypes both in vitro and in vivo. In addition, UC-MSC exosomes reversed PPARα level in ox-LDL-treated hepatocytes in vitro and in NASH mouse liver, which had been downregulated.
UC-MSC exosomes alleviate MCD-induced NASH in mice by regulating the anti-inflammatory phenotype of macrophages and by reversing PPARα protein expression in liver cells, which holds great potential in NASH therapy.
人脐带间充质干细胞（hUC-MSCs）因其良好的组织修复和抗炎作用，在终末期肝病的临床试验中越来越受到关注。hUC-MSC 外泌体是由产生它们的细胞分泌的具有球形结构的囊泡。外泌体的直径远小于 hUC-MSCs，这表明外泌体可能是间充质干细胞的一种新型、更安全的治疗产品。由于外泌体具有与 hUC-MSCs 相似的生化功能，本研究使用 MCD 诱导的小鼠模型研究了 hUC-MSC 衍生的外泌体在防治非酒精性脂肪性肝炎中的效率。
提取并纯化人脐带间充质干细胞衍生的外泌体。研究这些外泌体对 MCD 诱导的非酒精性脂肪性肝炎小鼠模型中疾病进展的影响。
结果表明，静脉注射到 MCD 诱导的 NASH 小鼠体内的 UC-MSC 外泌体改善了 MCD 诱导的体重减轻和肝损伤。此外，肝组织中的炎症细胞因子减少，这可能是外泌体在体外和体内诱导巨噬细胞抗炎表型所致。此外，UC-MSC 外泌体逆转了 ox-LDL 处理的肝细胞和 NASH 小鼠肝中下调的 PPARα 水平。
UC-MSC 外泌体通过调节巨噬细胞的抗炎表型和逆转肝细胞中 PPARα 蛋白表达，减轻 MCD 诱导的 NASH 小鼠的 NASH，在 NASH 治疗中具有巨大潜力。
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