■本研究检查了人类脂肪组织来源的间充质干细胞(hASCs)被修饰为过表达α-1抗胰蛋白酶(AAT)的保护潜力,在肝纤维化的小鼠模型中。
■对于终末期肝病的治疗,细胞疗法已成为肝移植的一种有希望的非侵入性替代方法。间充质干细胞(MSC)由于其促进肝脏再生和调节免疫系统的致病性炎症的双重能力而被评估。
■通过腹腔注射四氯化碳(CCl4)诱导小鼠肝纤维化。从人脂肪组织中提取MSC。在确认了干性之后,用含有AAT基因的慢病毒转导细胞,然后注射到老鼠的尾静脉。移植后14天,小鼠被处死,收集血液和组织样本进行分析。重要的肝酶,包括丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST),碱性磷酸酶(ALP),白蛋白,和总胆红素(TB),被测量。使用苏木精和曙红(H&E)进行组织学研究,以及马森三色(MT)染色。
■与hASCs相比,用AAT-hASCs治疗导致ALT更大程度的减少,AST,ALP,和TB,以及标准化的白蛋白水平。AAT-hASCs在组织学上促进肝脏再生增强,可能归因于AAT的抗炎和抗蛋白水解特性。
■这些发现表明AAT工程化hASCs是一种有前途的细胞基因治疗候选药物,可在肝硬化模型中进行进一步研究。
UNASSIGNED: The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.
UNASSIGNED: For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.
UNASSIGNED: Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice\'s tail vein. Fourteen days\' post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson\'s trichrome (MT) staining.
UNASSIGNED: Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.
UNASSIGNED: These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.