@article{8c34e58e14ad41dda487e94ab8856512,
title = "Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids",
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.",
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, Journal Article, Video-Audio Media",
author = "Fotios Sampaziotis and Justin, {Alexander W} and Tysoe, {Olivia C} and Stephen Sawiak and Godfrey, {Edmund M} and Upponi, {Sara S} and Gieseck, {Richard L} and {de Brito}, {Miguel Cardoso} and Berntsen, {Natalie Lie} and G{\'o}mez-V{\'a}zquez, {Mar{\'i}a J} and Daniel Ortmann and Loukia Yiangou and Alexander Ross and Johannes Bargehr and Alessandro Bertero and Zonneveld, {Mari{\"e}lle C F} and Pedersen, {Marianne T} and Matthias Pawlowski and Laura Valestrand and Pedro Madrigal and Nikitas Georgakopoulos and Negar Pirmadjid and Skeldon, {Gregor M} and John Casey and Wenmiao Shu and Materek, {Paulina M} and Snijders, {Kirsten E} and Brown, {Stephanie E} and Rimland, {Casey A} and Ingrid Simonic and Davies, {Susan E} and Jensen, {Kim B} and Matthias Zilbauer and Gelson, {William T H} and Alexander, {Graeme J} and Sanjay Sinha and Hannan, {Nicholas R F} and Wynn, {Thomas A} and Karlsen, {Tom H} and Espen Melum and Markaki, {Athina E} and Kourosh Saeb-Parsy and Ludovic Vallier",
year = "2017",
month = aug,
day = "1",
doi = "10.1038/nm.4360",
language = "English",
volume = "23",
pages = "954--963",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "nature publishing group",
number = "8",
}