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Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.


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.

SUBMITTER: Sampaziotis F 

PROVIDER: S-EPMC7610478 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

Sampaziotis Fotios F   Muraro Daniele D   Tysoe Olivia C OC   Sawiak Stephen S   Beach Timothy E TE   Godfrey Edmund M EM   Upponi Sara S SS   Brevini Teresa T   Wesley Brandon T BT   Garcia-Bernardo Jose J   Mahbubani Krishnaa K   Canu Giovanni G   Gieseck Richard R   Berntsen Natalie L NL   Mulcahy Victoria L VL   Crick Keziah K   Fear Corrina C   Robinson Sharayne S   Swift Lisa L   Gambardella Laure L   Bargehr Johannes J   Ortmann Daniel D   Brown Stephanie E SE   Osnato Anna A   Murphy Michael P MP   Corbett Gareth G   Gelson William T H WTH   Mells George F GF   Humphreys Peter P   Davies Susan E SE   Amin Irum I   Gibbs Paul P   Sinha Sanjay S   Teichmann Sarah A SA   Butler Andrew J AJ   See Teik Choon TC   Melum Espen E   Watson Christopher J E CJE   Saeb-Parsy Kourosh K   Vallier Ludovic L  

Science (New York, N.Y.) 20210201 6531


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  ...[more]

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