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Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease.

Authors :
Hallett JM
Ferreira-Gonzalez S
Man TY
Kilpatrick AM
Esser H
Thirlwell K
Macmillan MT
Rodrigo-Torres D
Dwyer BJ
Gadd VL
Ashmore-Harris C
Lu WY
Thomson JP
Jansen MA
O'Duibhir E
Starkey Lewis PJ
Campana L
Aird RE
Bate TSR
Fraser AR
Campbell JDM
Oniscu GC
Hay DC
Callanan A
Forbes SJ
Source :
Cell stem cell [Cell Stem Cell] 2022 Mar 03; Vol. 29 (3), pp. 355-371.e10.
Publication Year :
2022

Abstract

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.<br />Competing Interests: Declaration of interests S.J.F. and J.D.M.C. are founders and scientific advisors of Resolution Therapeutics Ltd (not related to this study). D.C.H. is a founder, director, and shareholder at Stemnovate Limited and Stimuliver ApS (not related to this study).<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1875-9777
Volume :
29
Issue :
3
Database :
MEDLINE
Journal :
Cell stem cell
Publication Type :
Academic Journal
Accession number :
35245467
Full Text :
https://doi.org/10.1016/j.stem.2022.02.006