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Characterization of...
Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease
- Artikel/kapitelEngelska2016
Förlag, utgivningsår, omfång ...
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2016-05-04
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Springer Science and Business Media LLC,2016
Nummerbeteckningar
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:133476585
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http://kipublications.ki.se/Default.aspx?queryparsed=id:133476585URI
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https://doi.org/10.1038/srep25187DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Hendriks, DFGKarolinska Institutet
(författare)
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Moro, SML
(författare)
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Ellis, EKarolinska Institutet
(författare)
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Walsh, J
(författare)
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Renblom, A
(författare)
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Puigvert, LF
(författare)
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Dankers, ACA
(författare)
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Jacobs, F
(författare)
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Snoeys, J
(författare)
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Sison-Young, RL
(författare)
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Jenkins, RE
(författare)
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Nordling, A
(författare)
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Mkrtchian, SKarolinska Institutet
(författare)
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Park, BK
(författare)
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Kitteringham, NR
(författare)
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Goldring, CEP
(författare)
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Lauschke, VMKarolinska Institutet
(författare)
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Ingelman-Sundberg, MKarolinska Institutet
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Scientific reports: Springer Science and Business Media LLC6, s. 25187-2045-2322
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Till lärosätets databas
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Bell, CC
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Hendriks, DFG
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Moro, SML
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Ellis, E
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Walsh, J
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Renblom, A
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visa fler...
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Puigvert, LF
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Dankers, ACA
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Jacobs, F
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Snoeys, J
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Sison-Young, RL
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Jenkins, RE
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Nordling, A
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Mkrtchian, S
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Park, BK
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Kitteringham, NR
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Goldring, CEP
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Lauschke, VM
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Ingelman-Sundber ...
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visa färre...
- Artiklar i publikationen
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Scientific repor ...
- Av lärosätet
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Karolinska Institutet