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Cholangiocyte organoids can repair bile ducts after transplantation in the human liver

Sampaziotis, F; Muraro, D; Tysoe, OC; Sawiak, S; Beach, TE; Godfrey, EM; Upponi, SS; ... Vallier, L; + view all (2021) Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science , 371 (6531) pp. 839-846. 10.1126/science.aaz6964. Green open access

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Abstract

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.

Type: Article
Title: Cholangiocyte organoids can repair bile ducts after transplantation in the human liver
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aaz6964
Publisher version: https://doi.org/10.1126/science.aaz6964
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10122962
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