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dc.contributor.authorRamachandran, Sarada Devi
dc.contributor.authorSchirmer, Katharina
dc.contributor.authorMünst, Bernhard
dc.contributor.authorHeinz, Stefan
dc.contributor.authorGhafoory, Shahrouz
dc.contributor.authorWölfl, Stefan
dc.contributor.authorSimon-Keller, Katja
dc.contributor.authorMarx, Alexander
dc.contributor.authorØie, Cristina Ionica
dc.contributor.authorEbert, Matthias P.
dc.contributor.authorWalles, Heike
dc.contributor.authorBraspenning, Joris
dc.contributor.authorBreitkopf-Heinlein, Katja
dc.date.accessioned2016-03-03T10:43:23Z
dc.date.available2016-03-03T10:43:23Z
dc.date.issued2015-10-21
dc.description.abstractIn this study we used differentiated adult human upcyte1 cells for the in vitro generation of liver organoids. Upcyte1 cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte1 process). Proliferating upcyte1 cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte1 cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.en_US
dc.identifier.citationPLoS ONE 2015, 10:e0139345(10)en_US
dc.identifier.cristinIDFRIDAID 1317096
dc.identifier.doi10.1371/journal.pone.0139345
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/8633
dc.identifier.urnURN:NBN:no-uit_munin_8253
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.titleIn vitro generation of functional liver organoid-like structures using adult human cellsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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