Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
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Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. / Sampaziotis, Fotios; Justin, Alexander W; Tysoe, Olivia C; Sawiak, Stephen; Godfrey, Edmund M; Upponi, Sara S; Gieseck, Richard L; de Brito, Miguel Cardoso; Berntsen, Natalie Lie; Gómez-Vázquez, María J; Ortmann, Daniel; Yiangou, Loukia; Ross, Alexander; Bargehr, Johannes; Bertero, Alessandro; Zonneveld, Mariëlle C F; Pedersen, Marianne T; Pawlowski, Matthias; Valestrand, Laura; Madrigal, Pedro; Georgakopoulos, Nikitas; Pirmadjid, Negar; Skeldon, Gregor M; Casey, John; Shu, Wenmiao; Materek, Paulina M; Snijders, Kirsten E; Brown, Stephanie E; Rimland, Casey A; Simonic, Ingrid; Davies, Susan E; Jensen, Kim B; Zilbauer, Matthias; Gelson, William T H; Alexander, Graeme J; Sinha, Sanjay; Hannan, Nicholas R F; Wynn, Thomas A; Karlsen, Tom H; Melum, Espen; Markaki, Athina E; Saeb-Parsy, Kourosh; Vallier, Ludovic.
In: Nature Medicine, Vol. 23, No. 8, 08.2017, p. 954-963.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
AU - Sampaziotis, Fotios
AU - Justin, Alexander W
AU - Tysoe, Olivia C
AU - Sawiak, Stephen
AU - Godfrey, Edmund M
AU - Upponi, Sara S
AU - Gieseck, Richard L
AU - de Brito, Miguel Cardoso
AU - Berntsen, Natalie Lie
AU - Gómez-Vázquez, María J
AU - Ortmann, Daniel
AU - Yiangou, Loukia
AU - Ross, Alexander
AU - Bargehr, Johannes
AU - Bertero, Alessandro
AU - Zonneveld, Mariëlle C F
AU - Pedersen, Marianne T
AU - Pawlowski, Matthias
AU - Valestrand, Laura
AU - Madrigal, Pedro
AU - Georgakopoulos, Nikitas
AU - Pirmadjid, Negar
AU - Skeldon, Gregor M
AU - Casey, John
AU - Shu, Wenmiao
AU - Materek, Paulina M
AU - Snijders, Kirsten E
AU - Brown, Stephanie E
AU - Rimland, Casey A
AU - Simonic, Ingrid
AU - Davies, Susan E
AU - Jensen, Kim B
AU - Zilbauer, Matthias
AU - Gelson, William T H
AU - Alexander, Graeme J
AU - Sinha, Sanjay
AU - Hannan, Nicholas R F
AU - Wynn, Thomas A
AU - Karlsen, Tom H
AU - Melum, Espen
AU - Markaki, Athina E
AU - Saeb-Parsy, Kourosh
AU - Vallier, Ludovic
PY - 2017/8
Y1 - 2017/8
N2 - 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 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 in vitro.
AB - 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 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 in vitro.
KW - Animals
KW - Bile Ducts, Extrahepatic
KW - Biliary Tract
KW - Cell Transplantation
KW - Cystic Fibrosis Transmembrane Conductance Regulator
KW - Epithelial Cells
KW - Gallbladder
KW - Humans
KW - In Vitro Techniques
KW - Keratin-19
KW - Keratin-7
KW - Mice
KW - Organoids
KW - Regeneration
KW - Secretin
KW - Somatostatin
KW - Tissue Engineering
KW - Tissue Scaffolds
KW - gamma-Glutamyltransferase
KW - Journal Article
KW - Video-Audio Media
U2 - 10.1038/nm.4360
DO - 10.1038/nm.4360
M3 - Journal article
C2 - 28671689
VL - 23
SP - 954
EP - 963
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 8
ER -
ID: 185436958