Biliary complications are a major challenge in liver transplantation, largely due to cholangiocytes being highly susceptible to cold-induced injury during organ preservation. Hibernating mammals, like Syrian hamsters, naturally tolerate deep hypothermia, protecting their organs from cold stress. In this study, scientists successfully established intrahepatic cholangiocyte organoids (shICOs) from Syrian hamsters and demonstrated that shICOs withstand cooling-rewarming stress better than mouse-derived mICOs. The key mechanism involves enhanced anti-ferroptosis ability, with shICOs maintaining lower ROS levels and lipid peroxidation under cold exposure.
Transcriptomic analysis revealed that, in addition to moderate upregulation of the lipid peroxidation defense gene Gpx4, shICOs exhibited higher expression of iron metabolism genes like Fth1 and Slc40a1, supporting more efficient iron homeostasis. Notably, adding iron chelator deferoxamine to preservation solutions improved mouse bile duct survival, suggesting translational potential. The shICO model thus offers a powerful tool for studying mammalian cold adaptation and developing optimized organ preservation protocols.
Key points of the study include:
- Syrian hamster cholangiocytes exhibit superior cold resistance compared to mice.
- Syrian hamster-derived cholangiocyte organoids (shICOs) survive cooling-rewarming stress better than mouse ICOs.
- shICOs possess stronger anti-ferroptosis capacity via efficient iron homeostasis.
- Iron chelation (e.g., deferoxamine) effectively alleviates biliary injury during cold storage
The work entitled "Insights of mammalian hibernator-derived cholangiocyte organoids in improving liver cold preservation" was published on Protein & Cell (published in 2025).
