Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.
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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.
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1095-9203
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Wellcome Trust (203151/Z/16/Z)
Medical Research Council (G0701448)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1)
British Heart Foundation (FS/18/46/33663)
Engineering and Physical Sciences Research Council (TS/H001220/1)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_17230)
National Institute for Health and Care Research (IS-BRC-1215-20014)
British Heart Foundation (PG/17/24/32886)
Medical Research Council (MC_PC_12012)