State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Pathology department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Sci Rep. 2024 Nov 1;14(1):26296. doi: 10.1038/s41598-024-77555-8.
Accumulating evidence has shown that adipose-derived stem cells (ADSCs) have the potential to differentiate into hepatic lineages, which are ideal engraftments for tissue-engineered repair. In this study, we investigated the potential of transplanted induced hepatocyte-like cells (iHEPs) in treating hepatic alveolar echinococcosis and describe an efficient three-step protocol for the generation of iHEPs in vitro from ADSCs. The expression of hepatocyte lineage markers was assessed and iHEPs function was evaluated by Periodic acid-Schiff staining. iHEPs were intravenously transplanted into mice infected with Echinococcus multilocularis. Histopathological analysis and liver function tests were used to assess therapeutic effects. The iHEPs exhibit morphological features and a glycogen storage function similar to those of mature hepatocytes and demonstrate an upregulation in hepatic gene programs with increasing induction time. Following transplantation, iHEPs were observed surrounding the metacestode lesions in the liver parenchyma of E. multilocularis-infected mice. iHEPs transplantation effectively restored liver function and improved liver injury in the infected mice. Additionally, we observed significant activation of the Wnt/β-catenin signaling pathway in the livers of infected mice transplanted with iHEPs. Our results provide evidence that iHEPs transplantation can alleviate E. multilocularis-induced liver injury, potentially creating new avenues for treating liver injury in end-stage hepatic alveolar echinococcosis.
越来越多的证据表明脂肪干细胞（ADSCs）具有向肝系分化的潜能，是组织工程修复的理想移植体。本研究探讨了诱导的肝细胞样细胞（iHEPs）移植治疗泡型包虫病的潜力，并描述了一种从 ADSCs 体外生成 iHEPs 的高效三步法方案。通过过碘酸希夫染色评估了肝细胞系标志物的表达，并评估了 iHEPs 的功能。将 iHEPs 静脉移植到感染多房棘球蚴的小鼠体内。通过组织病理学分析和肝功能试验评估治疗效果。iHEPs 表现出与成熟肝细胞相似的形态特征和糖原储存功能，并随着诱导时间的增加表现出肝基因程序的上调。移植后，在感染多房棘球蚴的小鼠肝实质中的包虫病病变周围观察到 iHEPs。iHEPs 移植可有效恢复感染小鼠的肝功能并改善肝损伤。此外，我们观察到在接受 iHEPs 移植的感染小鼠肝脏中 Wnt/β-catenin 信号通路显著激活。我们的研究结果为 iHEPs 移植可以减轻多房棘球蚴引起的肝损伤提供了证据，为治疗终末期泡型包虫病肝损伤提供了新的途径。
