Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids
Treatment of common bile duct disorders such as biliary atresia or ischaemic strictures is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here, we report a novel method for the isolation and propagation of human cholangiocytes fr...
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/43956/ |
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| author | 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 Brown, Stephanie 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 |
| author_facet | 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 Brown, Stephanie 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 |
| author_sort | Sampaziotis, Fotios |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Treatment of common bile duct disorders such as biliary atresia or ischaemic strictures is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here, we report a novel method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree and we explore the potential of bioengineered biliary tissue consisting of these extrahepatic cholangiocyte organoids (ECOs) and biodegradable scaffolds for transplantation and biliary reconstruction in vivo. ECOs closely correlate with primary cholangiocytes in terms of transcriptomic profile and functional properties (ALP, GGT). Following transplantation in immunocompromised mice ECOs self-organize into tubular structures expressing biliary markers (CK7). When seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary marker expression (CK7) and function (ALP, GGT). This bioengineered tissue can reconstruct the wall of the biliary tree (gallbladder) and rescue and extrahepatic biliary injury mouse model following transplantation. Furthermore, it can be fashioned into bioengineered ducts and replace the native common bile duct of immunocompromised mice, with no evidence of cholestasis or lumen occlusion up to one month after reconstruction. In conclusion, ECOs can successfully reconstruct the biliary tree following transplantation, providing proof-of-principle for organ regeneration using human primary cells expanded in vitro. |
| first_indexed | 2025-11-14T19:53:49Z |
| format | Article |
| id | nottingham-43956 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:53:49Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-439562020-05-04T18:53:53Z https://eprints.nottingham.ac.uk/43956/ 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 Brown, Stephanie 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 Treatment of common bile duct disorders such as biliary atresia or ischaemic strictures is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here, we report a novel method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree and we explore the potential of bioengineered biliary tissue consisting of these extrahepatic cholangiocyte organoids (ECOs) and biodegradable scaffolds for transplantation and biliary reconstruction in vivo. ECOs closely correlate with primary cholangiocytes in terms of transcriptomic profile and functional properties (ALP, GGT). Following transplantation in immunocompromised mice ECOs self-organize into tubular structures expressing biliary markers (CK7). When seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary marker expression (CK7) and function (ALP, GGT). This bioengineered tissue can reconstruct the wall of the biliary tree (gallbladder) and rescue and extrahepatic biliary injury mouse model following transplantation. Furthermore, it can be fashioned into bioengineered ducts and replace the native common bile duct of immunocompromised mice, with no evidence of cholestasis or lumen occlusion up to one month after reconstruction. In conclusion, ECOs can successfully reconstruct the biliary tree following transplantation, providing proof-of-principle for organ regeneration using human primary cells expanded in vitro. Nature Publishing Group 2017-07-03 Article PeerReviewed 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, Brown, Stephanie, 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 and Vallier, Ludovic (2017) Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine . ISSN 1546-170X Cholangiocytes Bile duct Bio-engineering Tissue engineering Organoids Regenerative medicine Cell-based therapy Biliary atresia PGA scaffold Collagen scaffold Densified collagen http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4360.html doi:10.1038/nm.4360 doi:10.1038/nm.4360 |
| spellingShingle | Cholangiocytes Bile duct Bio-engineering Tissue engineering Organoids Regenerative medicine Cell-based therapy Biliary atresia PGA scaffold Collagen scaffold Densified collagen 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 Brown, Stephanie 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 Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title | Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title_full | Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title_fullStr | Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title_full_unstemmed | Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title_short | Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| title_sort | reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids |
| topic | Cholangiocytes Bile duct Bio-engineering Tissue engineering Organoids Regenerative medicine Cell-based therapy Biliary atresia PGA scaffold Collagen scaffold Densified collagen |
| url | https://eprints.nottingham.ac.uk/43956/ https://eprints.nottingham.ac.uk/43956/ https://eprints.nottingham.ac.uk/43956/ |