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Numrering	Referens	Omslagsbild	Hitta
1.	Bell, CC, et al. (författare) Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease 2016 Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 25187- Tidskriftsartikel (refereegranskat)abstract 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.
2.	Pridgeon, CS, et al. (författare) Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms 2018 Ingår i: Archives of toxicology. - : Springer Science and Business Media LLC. - 1432-0738 .- 0340-5761. ; 92:2, s. 557-569 Tidskriftsartikel (refereegranskat)
3.	Sison-Young, RLC, et al. (författare) Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication 2015 Ingår i: Toxicological sciences : an official journal of the Society of Toxicology. - : Oxford University Press (OUP). - 1096-0929. ; 147:2, s. 412-424 Tidskriftsartikel (refereegranskat)

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Resultat 1-3 av 3

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Typ av publikation: tidskriftsartikel (3)

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Författare/redaktör: Park, BK (3); Goldring, CEP (3); Ingelman-Sundberg, M (2); Hendriks, DFG (2); Sison-Young, RL (2); Jenkins, RE (2); visa fler...; Kitteringham, NR (2); Lauschke, VM (1); Ellis, E (1); Walsh, J. (1); Walker, P (1); Mkrtchian, S (1); Nordling, A (1); Ansari, T (1); Richert, L (1); Bell, CC (1); Moro, SML (1); Renblom, A (1); Puigvert, LF (1); Dankers, ACA (1); Jacobs, F (1); Snoeys, J (1); Heckel, T. (1); Cross, MJ (1); Hewitt, PG (1); Weaver, RJ (1); Gibbs, S (1); Przyborski, S (1); Pridgeon, CS (1); Jones, RP (1); Heringa, MB (1); Mottram, D (1); Wong, MW (1); Launay, L (1); Schlott, C (1); Leedale, J (1); Gryshkova, V (1); Bearon, RN (1); Wilkinson, EL (1); Greenman, J (1); Sidaway, J (1); Johann, E (1); Alexandre, E (1); Aerts, H (1); Sison-Young, RLC (1); Mitsa, D (1); visa färre...

Lärosäte: Karolinska Institutet (3)

Språk: Engelska (3)

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