Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium.

类器官技术为再生医学带来了巨大希望，但尚未应用于人类。我们在胆管病的背景下使用胆管细胞类器官来应对这一挑战，这是肝移植的一个关键原因。使用单细胞 RNA 测序，我们表明原代人胆管细胞显示出在类器官培养中丢失的转录多样性。然而，胆管细胞类器官保持可塑性，并在移植回胆管树时恢复其体内特征。然后，我们利用接受离体常温灌注的人体肝脏细胞移植模型来证明这种特性允许肝外类器官在移植后修复人体肝内导管。