Tools
Tools
Gaskell, H, Sharma, P, Colley, HE, Murdoch, C, Williams, DP and Webb, SD (2016) Characterization of a functional C3A liver spheroid model. Toxicology Research, 5. pp. 1053-1065. ISSN 2045-452X
|
Text
GaskellCFC2016.pdf - Accepted Version Download (2MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Science & Technology; Life Sciences & Biomedicine; Toxicology; IN-VITRO MODEL; DRUG-METABOLISM; 3D SPHEROIDS; HEPATOCYTE SPHEROIDS; TETHERED SPHEROIDS; CELL SPHEROIDS; TOXICITY; CULTURE; EXPRESSION; INJURY |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Applied Mathematics (merged with Comp Sci 10 Aug 20) |
| Publisher: | Royal Society of Chemistry |
| Related URLs: | |
| Date Deposited: | 19 Sep 2017 11:26 |
| Last Modified: | 04 Sep 2021 11:21 |
| DOI or ID number: | 10.1039/c6tx00101g |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/6823 |
 |
View Item |