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Extension of the Virtual Cell Based Assay from a 2-D to a 3-D Cell Culture Model

Tijdschriftbijdrage - Tijdschriftartikel

Prediction of chemical toxicity is very useful in risk assessment. With the current paradigm shift towards the use of in vitro and in silico systems, we present herein a theoretical mathematical description of a quasi-diffusion process to predict chemical concentrations in 3-D spheroid cell cultures. By extending a 2-D Virtual Cell Based Assay (VCBA) model into a 3-D spheroid cell model, we assume that cells are arranged in a series of concentric layers within the sphere. We formulate the chemical quasi-diffusion process by simplifying the spheroid with respect to the number of cells in each layer. The system was calibrated and tested with acetaminophen (APAP). Simulated predictions of APAP toxicity were compared with empirical data from in vitro measurements by using a 3-D spheroid model. The results of this first attempt to extend the VCBA model are promising - they show that the VCBA model simulates close correlation between the influence of compound concentration and the viability of the HepaRG 3-D cell culture. The 3-D VCBA model provides a complement to current in vitro procedures to refine experimental setups, to fill data gaps and help in the interpretation of in vitro data for the purposes of risk assessment.

Tijdschrift: Alternatives to Laboratory Animals
ISSN: 0261-1929
Issue: 1
Volume: 50
Pagina's: 45-56
Jaar van publicatie:2022
Trefwoorden:HepaRG, chemical exposure, distribution model, fate modelling, in silico, in vitro, mathematical modelling, multiscale cell culture, spheroids
Toegankelijkheid:Open