Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis

Abstract

Abstract 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.

Keywords

• Hepatocyte-like cells
• Adipose-derived stem cells
• Echinococcus multilocularis
• Liver injury