Program Doktor Ilmu Biomedik, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Department of Histology, Faculty of Medicine, Universitas Gunadarma, Depok, Indonesia.
In Vitro Cell Dev Biol Anim. 2023 Dec;59(10):747-763. doi: 10.1007/s11626-023-00817-8. Epub 2023 Dec 18.
The present study aimed to develop viable liver organoids using decellularized native liver scaffolds and evaluate the efficacy of human liver organoid transplantation in a rabbit model of cirrhosis. Liver organoids were formed by coculture of hepatocyte-like cells derived from the human-induced pluripotent stem cells with three other cell types. Twelve 3-mo-old New Zealand White Rabbits underwent a sham operation, bile duct ligation, or biliary duct ligation followed by liver organoid transplantation. Liver organoid structure and function before and after transplantation were evaluated using histological and molecular analyses. A survival analysis using the Kaplan-Meier method was performed to determine the cumulative probability of survival according to liver organoid transplantation with significantly greater overall survival observed in rabbits that underwent liver organoid transplantation (P = 0.003, log-rank test). The short-term group had higher hepatic expression levels of ALB and CYP3A mRNA and lower expression levels of AST mRNA compared to the long-term group. The short-term group also had lower collagen deposition in liver tissues. Transplantation of human liver organoids cocultured in decellularized native liver scaffold into rabbits that had undergone bile duct ligation improved short-term survival and hepatic function. The results of the present study highlight the potential of liver organoid transplantation as a bridging therapy in liver failure; however, rejection and poor liver organoid function may limit the long-term efficacy of this therapeutic approach.
本研究旨在使用脱细胞天然肝脏支架构建可行的肝脏类器官，并评估人肝脏类器官移植在肝硬化兔模型中的疗效。肝脏类器官是通过将人诱导多能干细胞来源的肝样细胞与另外三种细胞共培养而形成的。12 只 3 月龄新西兰白兔接受假手术、胆管结扎或胆管结扎后肝类器官移植。使用组织学和分子分析评估移植前后肝类器官的结构和功能。采用 Kaplan-Meier 生存分析法根据肝类器官移植确定累积生存率，肝类器官移植组的总生存率明显更高（P=0.003，对数秩检验）。短期组的 ALB 和 CYP3A mRNA 肝表达水平较高，AST mRNA 表达水平较低。短期组肝组织胶原沉积也较低。将在脱细胞天然肝脏支架中培养的人肝脏类器官移植到接受胆管结扎的兔体内，可提高短期生存率和肝功能。本研究结果强调了肝类器官移植作为肝衰竭桥接治疗的潜力；然而，排斥反应和肝类器官功能不良可能限制这种治疗方法的长期疗效。
