Cholangiocyte organoids can repair bile ducts after transplantation in the human liver
Fotios Sampaziotis, Daniele Muraro, Olivia Tysoe, Stephen J. Sawiak, Timothy E. Beach, Edmund Godfrey, Sara Upponi, Teresa Brevini, Brandon T. Wesley, José Garcia‐Bernardo, Krishnaa T. Mahbubani, Giovanni Canu, Richard L. Gieseck, Natalie Lie Berntsen, Victoria Mulcahy, Keziah Crick, Corrina Fear, Sharayne Robinson, Lisa Swift, Laure Gambardella, Johannes Bargehr, Daniel Ortmann, Stephanie Brown, Anna Osnato, Michael P. Murphy, Gareth Corbett, William Gelson, George Mells, Peter Humphreys, Susan Davies, Irum Amin, Paul Gibbs, Sanjay Sinha, Sarah A. Teichmann, Andrew J. Butler, Teik Choon See, Espen Melum, Christopher J.E. Watson, Kourosh Saeb‐Parsy, Ludovic Vallier
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.