Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation
The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangioc...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2015
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| Online Access: | https://eprints.nottingham.ac.uk/43037/ |
| _version_ | 1848796628479115264 |
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| author | Sampaziotis, Fotios Cardoso de Brito, Miguel Madrigal, Pedro Bertero, Alessandro Saeb-Parsy, Kourosh Soares, Filipa A.C. Schrumpf, Elisabeth Melum, Espen Karlsen, Tom H. Bradley, J. Andrew Gelson, William T.H. Davies, Susan Baker, Alastair Kaser, Arthur Alexander, Graeme J. Hannan, Nicholas R.F. Vallier, Ludovic |
| author_facet | Sampaziotis, Fotios Cardoso de Brito, Miguel Madrigal, Pedro Bertero, Alessandro Saeb-Parsy, Kourosh Soares, Filipa A.C. Schrumpf, Elisabeth Melum, Espen Karlsen, Tom H. Bradley, J. Andrew Gelson, William T.H. Davies, Susan Baker, Alastair Kaser, Arthur Alexander, Graeme J. Hannan, Nicholas R.F. Vallier, Ludovic |
| author_sort | Sampaziotis, Fotios |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening. |
| first_indexed | 2025-11-14T19:51:00Z |
| format | Article |
| id | nottingham-43037 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:51:00Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-430372020-05-04T17:10:48Z https://eprints.nottingham.ac.uk/43037/ Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation Sampaziotis, Fotios Cardoso de Brito, Miguel Madrigal, Pedro Bertero, Alessandro Saeb-Parsy, Kourosh Soares, Filipa A.C. Schrumpf, Elisabeth Melum, Espen Karlsen, Tom H. Bradley, J. Andrew Gelson, William T.H. Davies, Susan Baker, Alastair Kaser, Arthur Alexander, Graeme J. Hannan, Nicholas R.F. Vallier, Ludovic The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening. Nature Publishing Group 2015-06-13 Article PeerReviewed Sampaziotis, Fotios, Cardoso de Brito, Miguel, Madrigal, Pedro, Bertero, Alessandro, Saeb-Parsy, Kourosh, Soares, Filipa A.C., Schrumpf, Elisabeth, Melum, Espen, Karlsen, Tom H., Bradley, J. Andrew, Gelson, William T.H., Davies, Susan, Baker, Alastair, Kaser, Arthur, Alexander, Graeme J., Hannan, Nicholas R.F. and Vallier, Ludovic (2015) Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology, 33 (8). pp. 845-852. ISSN 1546-1696 https://www.nature.com/nbt/journal/v33/n8/full/nbt.3275.html doi:10.1038/nbt.3275 doi:10.1038/nbt.3275 |
| spellingShingle | Sampaziotis, Fotios Cardoso de Brito, Miguel Madrigal, Pedro Bertero, Alessandro Saeb-Parsy, Kourosh Soares, Filipa A.C. Schrumpf, Elisabeth Melum, Espen Karlsen, Tom H. Bradley, J. Andrew Gelson, William T.H. Davies, Susan Baker, Alastair Kaser, Arthur Alexander, Graeme J. Hannan, Nicholas R.F. Vallier, Ludovic Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title | Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title_full | Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title_fullStr | Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title_full_unstemmed | Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title_short | Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| title_sort | cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation |
| url | https://eprints.nottingham.ac.uk/43037/ https://eprints.nottingham.ac.uk/43037/ https://eprints.nottingham.ac.uk/43037/ |