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Isolation and propagation of primary human cholangiocyte organoids for the generation of bioengineered biliary tissue.

Accepted version
Peer-reviewed

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Authors

Tysoe, Olivia C 
Justin, Alexander W 
Brevini, Teresa 
Chen, Si Emma 
Mahbubani, Krishnaa T 

Abstract

Pediatric liver transplantation is often required as a consequence of biliary disorders because of the lack of alternative treatments for repairing or replacing damaged bile ducts. To address the lack of availability of pediatric livers suitable for transplantation, we developed a protocol for generating bioengineered biliary tissue suitable for biliary reconstruction. Our platform allows the derivation of cholangiocyte organoids (COs) expressing key biliary markers and retaining functions of primary extra- or intrahepatic duct cholangiocytes within 2 weeks of isolation. COs are subsequently seeded on polyglycolic acid (PGA) scaffolds or densified collagen constructs for 4 weeks to generate bioengineered tissue retaining biliary characteristics. Expertise in organoid culture and tissue engineering is desirable for optimal results. COs correspond to mature functional cholangiocytes, differentiating our method from alternative organoid systems currently available that propagate adult stem cells. Consequently, COs provide a unique platform for studies in biliary physiology and pathophysiology, and the resulting bioengineered tissue has broad applications for regenerative medicine and cholangiopathies.

Description

Keywords

Animals, Bile Ducts, Biocompatible Materials, Cell Separation, Cells, Cultured, Equipment Design, Humans, Mice, Organoids, Regeneration, Tissue Engineering, Tissue Scaffolds

Journal Title

Nat Protoc

Conference Name

Journal ISSN

1754-2189
1750-2799

Volume Title

14

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Isaac Newton Trust (18.07i(c))
Engineering and Physical Sciences Research Council (EP/N509620/1)
MRC (1621144)
Medical Research Council (MC_PC_12009)
Academy of Medical Sciences (SGL019\1071)
European Research Council (741707)