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Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation

Open access
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·2015·Nature Biotechnology

Abstract

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.

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Metadata

Authors
Sampaziotis, F., Cardoso de Brito, M., Madrigal, P., Bertero, A., Saeb-Parsy, K., Soares, F. A. C., Schrumpf, E., Melum, E., Karlsen, T. H., Bradley, J. A., Gelson, W. T. H., Davies, S., Baker, A., Kaser, A., Alexander, G. J., Hannan, N. R. F., & Vallier, L.
Venue
Nature Biotechnology
Published
2015-07-13
Volume
33
Issue
8
Pages
845-852
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2201543151
Cited by
397
References
5
FWCI
13.51
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. https://app.cochat.ai/papers/10.1038/nbt.3275
The paper
Sampaziotis, F., Cardoso de Brito, M., Madrigal, P., Bertero, A., Saeb-Parsy, K., Soares, F. A. C., Schrumpf, E., Melum, E., Karlsen, T. H., Bradley, J. A., Gelson, W. T. H., Davies, S., Baker, A., Kaser, A., Alexander, G. J., Hannan, N. R. F., & Vallier, L. (2015). Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology. https://doi.org/10.1038/nbt.3275

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.