CUED Publications database

Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids

Sampaziotis, F and Justin, AW and Tysoe, OC and Sawiak, S and Cardoso-de-Brito, M and Ortmann, D and Yangou, L and Ross, A and Bargher, J and Bertero, A and Zonneveld, MCF and Pawlowski, M and Madrigal, P and Georgakopoulos, N and Pirmadjid, N and zilbauer, M and Sinha, S and Hannan, NRF and Vallier, L (2017) Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine.

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Abstract

The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids $\textit{in vivo}$ and demonstrate that ECOs self-organize into bile duct–like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded $\textit{in vitro}$.

Item Type: Article
Uncontrolled Keywords: regenerative medicine tissue engineering
Subjects: UNSPECIFIED
Divisions: Div C > Biomechanics
Depositing User: Cron Job
Date Deposited: 17 Jul 2017 19:05
Last Modified: 16 Nov 2017 02:10
DOI: