Organoids grown from bile duct epithelial cells can be used to repair damaged bile ducts in transplanted human livers, researchers report. The results provide proof of concept for using ex vivo cell-based therapy to improve organ function before transplantation, which could ultimately increase the number of useable organs on the transplant waiting list. Bile produced in the liver is carried to the small intestine through a network of bile ducts formed by biliary epithelial cells known as cholangiocytes. While crucial for digestion, bile becomes toxic when it accumulates in the liver. As a result, chronic liver diseases that affect cholangiocytes often result in liver failure and account for a significant number of human liver transplants. Though liver donors are almost always in short supply, organoid technology holds great promise for regenerative medicine and is often considered as a potential alternative to liver transplantation for biliary diseases. However, in vivo engraftment, survival and function of organoids in humans has yet to be established. Using single-cell RNA sequencing and a mouse model of biliary injury, Fotios Sampaziotis and colleagues found that organoids grown from primary human cholangiocytes retain their plasticity, allowing cells from one region to repair different regions of the biliary tree. Sampaziotis et al. transplanted cholangiocyte organoids into the intrahepatic ducts of deceased human donor livers undergoing normothermic perfusion - a technique used to keep organs alive outside the human body - and found that the engrafted organoids repaired bile ducts in the ex vivo livers. The findings provide proof of concept that cholangiocytes from non-diseased areas, such as the gallbladder, could be used in cell-based therapies for cholangiopathies affecting bile ducts within the liver. The findings bring "cell therapy for intrahepatic biliary disease a step closer to clinical translation," write Simone Kurial and Holder Willenbring in a related Perspective.