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Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

Sampaziotis, F; Justin, AW; Tysoe, OC; Sawiak, S; Godfrey, EM; Upponi, SS; Gieseck, RL; ... Vallier, L; + view all (2017) Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine , 23 (8) pp. 954-963. 10.1038/nm.4360. Green open access

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Abstract

The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct-like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro.

Type: Article
Title: Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nm.4360
Publisher version: https://doi.org/10.1038/nm.4360
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.
Keywords: Animals, Bile Ducts, Extrahepatic, Biliary Tract, Cell Transplantation, Cystic Fibrosis Transmembrane Conductance Regulator, Epithelial Cells, Gallbladder, Humans, In Vitro Techniques, Keratin-19, Keratin-7, Mice, Organoids, Regeneration, Secretin, Somatostatin, Tissue Engineering, Tissue Scaffolds, gamma-Glutamyltransferase
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 Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10077126
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