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Characterization of a functional C3A liver spheroid model

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Toxicology Research Vol - 5 Issue - 3

Toxicology Research Vol - 5 Issue - 2

Toxicology Research Vol - 5 Issue - 1

Toxicology Research Vol -4

Toxicology Research Vol -3

Toxicology Research Vol -2

Toxicology Research Vol -1

Characterization of a functional C3A liver spheroid model

Content Provider	Royal Society of Chemistry (RSC)
Author	Murdoch, Craig Sharma, Parveen Gaskell, Harriet Colley, Helen E. Webb, Steven D. Williams, Dominic P.
Copyright Year	2016
Abstract	More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells. Spheroids were viable and maintained a compact in vivo-like structure with zonation features for up to 32 days. MRP2 and Pgp transporters had polarised expression on the canalicular membrane of cells in the spheroids and were able to functionally transport CMFDA substrate into these canalicular structures. Spheroids expressed CYP2E1 and were able to synthesise and secrete albumin and urea to a higher degree than monolayer C3A cultures. Penetration of doxorubicin throughout the spheroid core was demonstrated. Spheroids showed increased susceptibility to hepatotoxins when compared to 2D cultures, with acetaminophen having an IC50 of 7.2 mM in spheroids compared to 33.8 mM in monolayer culture. To conclude, we developed an alternative method for creating C3A liver spheroids and demonstrated cellular polarisation and zonation, as well as superior liver-specific functionality and more sensitive toxicological response compared to standard 2D liver models, confirming a more in vivo-like liver model.
Starting Page	1053
Ending Page	1065
Page Count	13
File Format	HTM / HTML PDF
ISSN	2045452X
Volume Number	5
Issue Number	4
Journal	Toxicology Research
DOI	10.1039/c6tx00101g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Urea Paracetamol Liver IC50 Pgp Albumin Spheroid CYP2E1 Hepatotoxicity Doxorubicin Three-dimensional space
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Toxicology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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Characterization of a functional C3A liver spheroid model

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