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dc.contributor.authorSampaziotis, Fotiosen
dc.contributor.authorde, Brito Miguel Cardosoen
dc.contributor.authorMadrigal, Pedroen
dc.contributor.authorBertero, Alessandroen
dc.contributor.authorSaeb-Parsy, Kouroshen
dc.contributor.authorSoares, Filipaen
dc.contributor.authorSchrumpf, Elisabethen
dc.contributor.authorMelum, Espenen
dc.contributor.authorKarlsen, Tom Hen
dc.contributor.authorBradley, Johnen
dc.contributor.authorGelson, William THen
dc.contributor.authorDavies, Susanen
dc.contributor.authorBaker, Alastairen
dc.contributor.authorKaser, Arthuren
dc.contributor.authorAlexander, Graeme Jen
dc.contributor.authorHanna, Nicholas RFen
dc.contributor.authorVallier, Ludovicen
dc.date.accessioned2015-06-23T11:44:47Z
dc.date.available2015-06-23T11:44:47Z
dc.date.issued2015-06-23en
dc.identifier.citationSampaziotis et al. Nature Biotechnology (2015) Vol. 33, pp. 845-852. doi:10.1038/nbt.3275 (2015)en
dc.identifier.issn1087-0156
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/248631
dc.description.abstractThe 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, gamma-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and VEGF. 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.
dc.description.sponsorshipThis work was funded by ERC starting grant Relieve IMDs (L.V., N.H.), the Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V., N.H., F.S.), the Evelyn trust (N.H.) and the EU Fp7 grant TissuGEN (M.CDB.). FS has been supported by an Addenbrooke’s Charitable Trust Clinical Research Training Fellowship and a joint MRC-Sparks Clinical Research Training Fellowship.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNPG
dc.titleCholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validationen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nbt.3275en
prism.endingPage852
prism.publicationDate2015en
prism.publicationNameNature Biotechnologyen
prism.startingPage845
prism.volume33en
dc.rioxxterms.funderERC
dc.rioxxterms.funderNIHR
dc.rioxxterms.funderMRC
dcterms.dateAccepted2015-06-05en
rioxxterms.versionofrecord10.1038/nbt.3275en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-06-23en
dc.contributor.orcidMadrigal, Pedro [0000-0003-1959-8199]
dc.contributor.orcidSaeb-Parsy, Kourosh [0000-0002-0633-3696]
dc.contributor.orcidVallier, Ludovic [0000-0002-3848-2602]
dc.identifier.eissn1546-1696
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/L016761/1)
pubs.funder-project-idMRC (G1000847)
pubs.funder-project-idEuropean Research Council (281335)
pubs.funder-project-idMRC (G0800784)
rioxxterms.freetoread.startdate2016-01-13


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