Modeling ischemic-type biliary lesion in vitro using human expandable intrahepatic cholangiocyte organoids

Ischemic-type biliary lesion (ITBL) remains one of the most common complications following liver transplantation. It is imperative to further explore the occurrence and development mechanism of ITBL. Intrahepatic cholangiocyte organoids (ICOs) derived from human liver tissue replicate the structure and function of bile ducts and serve as an innovative experimental tool for in vitro modeling of cholangiopathies.

In this study, ICOs derived from human liver tissue were cultured under ischemia and hypoxia (IH) conditions to establish an in vitro model of ITBL. Immunofluorescence staining, RT-qPCR, Western blotting, and transcriptomic analysis were performed to investigate the effects of IH on ICOs and evaluate the validity of the ITBL model.

IH significantly reduced the diameter and cell viability of ICOs. After exposure to IH for more than 48 h, the proliferation of ICOs decreased, accompanied by increased inflammatory responses and apoptosis. Transcriptomic analysis revealed a landscape of pathophysiological genetic changes in the ITBL model in response to IH.

We have presented a novel ITBL model constructed using expandable human ICOs, which is of great significance for exploring the molecular mechanism and potential therapeutic targets of ITBL.