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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
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Bell, CC (författare)
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- Hendriks, DFG (författare)
- Karolinska Institutet
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Moro, SML (författare)
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visa fler...
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- Ellis, E (författare)
- Karolinska Institutet
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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, S (författare)
- Karolinska Institutet
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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, VM (författare)
- Karolinska Institutet
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- Ingelman-Sundberg, M (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-05-04
- 2016
- Engelska.
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 25187-
- Relaterad länk:
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https://www.nature.c...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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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.
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Till lärosätets databas
- Av författaren/redakt...
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Bell, CC
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Hendriks, DFG
-
Moro, SML
-
Ellis, E
-
Walsh, J
-
Renblom, A
-
visa fler...
-
Puigvert, LF
-
Dankers, ACA
-
Jacobs, F
-
Snoeys, J
-
Sison-Young, RL
-
Jenkins, RE
-
Nordling, A
-
Mkrtchian, S
-
Park, BK
-
Kitteringham, NR
-
Goldring, CEP
-
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