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dc.contributor.authorGeorgakopoulos, Nikitas
dc.contributor.authorPrior, Nicole
dc.contributor.authorAngres, Brigitte
dc.contributor.authorMastrogiovanni, Gianmarco
dc.contributor.authorCagan, Alex
dc.contributor.authorHarrison, Daisy
dc.contributor.authorHindley, Christopher J
dc.contributor.authorArnes-Benito, Robert
dc.contributor.authorLiau, Siong-Seng
dc.contributor.authorCurd, Abbie
dc.contributor.authorIvory, Natasha
dc.contributor.authorSimons, Benjamin D
dc.contributor.authorMartincorena, Inigo
dc.contributor.authorWurst, Helmut
dc.contributor.authorSaeb-Parsy, Kourosh
dc.contributor.authorHuch, Meritxell
dc.date.accessioned2020-03-29T01:38:24Z
dc.date.available2020-03-29T01:38:24Z
dc.date.issued2020-02-26
dc.identifier.issn1471-213X
dc.identifier.otherPMC7043048
dc.identifier.other32098630
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303876
dc.description.abstractBACKGROUND:Pancreatic organoid systems have recently been described for the in vitro culture of pancreatic ductal cells from mouse and human. Mouse pancreatic organoids exhibit unlimited expansion potential, while previously reported human pancreas organoid (hPO) cultures do not expand efficiently long-term in a chemically defined, serum-free medium. We sought to generate a 3D culture system for long-term expansion of human pancreas ductal cells as hPOs to serve as the basis for studies of human pancreas ductal epithelium, exocrine pancreatic diseases and the development of a genomically stable replacement cell therapy for diabetes mellitus. RESULTS:Our chemically defined, serum-free, human pancreas organoid culture medium supports the generation and expansion of hPOs with high efficiency from both fresh and cryopreserved primary tissue. hPOs can be expanded from a single cell, enabling their genetic manipulation and generation of clonal cultures. hPOs expanded for months in vitro maintain their ductal morphology, biomarker expression and chromosomal integrity. Xenografts of hPOs survive long-term in vivo when transplanted into the pancreas of immunodeficient mice. Notably, mouse orthotopic transplants show no signs of tumorigenicity. Crucially, our medium also supports the establishment and expansion of hPOs in a chemically defined, modifiable and scalable, biomimetic hydrogel. CONCLUSIONS:hPOs can be expanded long-term, from both fresh and cryopreserved human pancreas tissue in a chemically defined, serum-free medium with no detectable tumorigenicity. hPOs can be clonally expanded, genetically manipulated and are amenable to culture in a chemically defined hydrogel. hPOs therefore represent an abundant source of pancreas ductal cells that retain the characteristics of the tissue-of-origin, which opens up avenues for modelling diseases of the ductal epithelium and increasing understanding of human pancreas exocrine biology as well as for potentially producing insulin-secreting cells for the treatment of diabetes.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1471-213X
dc.sourcenlmid: 100966973
dc.subjectPancreas
dc.subjectGenetic stability
dc.subjectOrganoid
dc.subjectChemically Defined Hydrogel
dc.subjectPrimary Cultures
dc.subjectIn Vivo Safety
dc.titleLong-term expansion, genomic stability and in vivo safety of adult human pancreas organoids.
dc.typeArticle
dc.date.updated2020-03-29T01:38:23Z
prism.issueIdentifier1
prism.publicationNameBMC developmental biology
prism.volume20
dc.identifier.doi10.17863/CAM.50958
rioxxterms.versionofrecord10.1186/s12861-020-0209-5
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidPrior, Nicole [0000-0003-2856-7052]
dc.contributor.orcidHuch, Meritxell [0000-0002-1545-5265]
pubs.funder-project-idCancer Research UK (C6946/A14492, 21777)
pubs.funder-project-idWellcome Trust (104151/Z/14/Z, 092096, 104151)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International