作者
Fotios Sampaziotis, Daniele Muraro, Olivia C Tysoe, Stephen Sawiak, Timothy E Beach, Edmund M Godfrey, Sara S Upponi, Teresa Brevini, Brandon T Wesley, Jose Garcia-Bernardo, Krishnaa Mahbubani, Giovanni Canu, Richard Gieseck III, Natalie L Berntsen, Victoria L Mulcahy, Keziah Crick, Corrina Fear, Sharayne Robinson, Lisa Swift, Laure Gambardella, Johannes Bargehr, Daniel Ortmann, Stephanie E Brown, Anna Osnato, Michael P Murphy, Gareth Corbett, William TH Gelson, George F Mells, Peter Humphreys, Susan E Davies, Irum Amin, Paul Gibbs, Sanjay Sinha, Sarah A Teichmann, Andrew J Butler, Teik Choon See, Espen Melum, Christopher JE Watson, Kourosh Saeb-Parsy, Ludovic Vallier
发表日期
2021/2/19
期刊
Science
卷号
371
期号
6531
页码范围
839-846
出版商
American Association for the Advancement of Science
简介
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.
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