| Literature DB >> 33602855 |
Kourosh Saeb-Parsy1,2, Ludovic Vallier3,1, Fotios Sampaziotis3,4,5, Daniele Muraro6, Olivia C Tysoe6,1, Stephen Sawiak7, Timothy E Beach1, Edmund M Godfrey8, Sara S Upponi8, Teresa Brevini6, Brandon T Wesley6, Jose Garcia-Bernardo9, Krishnaa Mahbubani1, Giovanni Canu6, Richard Gieseck10, Natalie L Berntsen11,12,13, Victoria L Mulcahy4,14, Keziah Crick2, Corrina Fear2, Sharayne Robinson2, Lisa Swift2, Laure Gambardella6,4, Johannes Bargehr6,4,15, Daniel Ortmann6, Stephanie E Brown6, Anna Osnato6, Michael P Murphy16, Gareth Corbett17, William T H Gelson4,5, George F Mells4,5,14, Peter Humphreys6, Susan E Davies18, Irum Amin1,2, Paul Gibbs1,2, Sanjay Sinha6,4, Sarah A Teichmann9,19, Andrew J Butler1,2, Teik Choon See8, Espen Melum11,12,13,20,21, Christopher J E Watson1,2,22,23.
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.Entities:
Mesh：
Year: 2021 PMID： 33602855 PMCID： PMC7610478 DOI： 10.1126/science.aaz6964
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728