TY  - JOUR
N2  - 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.
ID  - discovery10122962
UR  - https://doi.org/10.1126/science.aaz6964
JF  - Science
A1  - Sampaziotis, F
A1  - Muraro, D
A1  - Tysoe, OC
A1  - Sawiak, S
A1  - Beach, TE
A1  - Godfrey, EM
A1  - Upponi, SS
A1  - Brevini, T
A1  - Wesley, BT
A1  - Garcia-Bernardo, J
A1  - Mahbubani, K
A1  - Canu, G
A1  - Gieseck, R
A1  - Berntsen, NL
A1  - Mulcahy, VL
A1  - Crick, K
A1  - Fear, C
A1  - Robinson, S
A1  - Swift, L
A1  - Gambardella, L
A1  - Bargehr, J
A1  - Ortmann, D
A1  - Brown, SE
A1  - Osnato, A
A1  - Murphy, MP
A1  - Corbett, G
A1  - Gelson, WTH
A1  - Mells, GF
A1  - Humphreys, P
A1  - Davies, SE
A1  - Amin, I
A1  - Gibbs, P
A1  - Sinha, S
A1  - Teichmann, SA
A1  - Butler, AJ
A1  - See, TC
A1  - Melum, E
A1  - Watson, CJE
A1  - Saeb-Parsy, K
A1  - Vallier, L
TI  - Cholangiocyte organoids can repair bile ducts after transplantation in the human liver
VL  - 371
AV  - public
SP  - 839
Y1  - 2021/02/19/
EP  - 846
IS  - 6531
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ER  -