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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


Fotios Sampaziotis

Miguel Cardoso de Brito

Pedro Madrigal

Alessandro Bertero

Kourosh Saeb-Parsy

Filipa A.C. Soares

Elisabeth Schrumpf

Espen Melum

Tom H. Karlsen

J. Andrew Bradley

William T.H. Gelson

Susan Davies

Alastair Baker

Arthur Kaser

Graeme J. Alexander

Ludovic Vallier


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.


Sampaziotis, F., Cardoso de Brito, M., Madrigal, P., Bertero, A., Saeb-Parsy, K., Soares, F. A., …Vallier, L. (in press). Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology, 33(8), doi:10.1038/nbt.3275

Journal Article Type Article
Acceptance Date Jun 5, 2015
Online Publication Date Jun 13, 2015
Deposit Date May 23, 2017
Journal Nature Biotechnology
Print ISSN 1087-0156
Electronic ISSN 1546-1696
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 33
Issue 8
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address: