Extension of the virtual cell based assay from a 2D to a 3D cell-culture model

Prediction of toxicity is very important in risk assessment. With the current paradigm shift towards utilization of in-vitro and in-silico systems we present herein a theoretical mathematical description of a quasi-diffusion process to predict chemical concentration in 3D spheroid cell cultures. By expanding a 2D Virtual Cell Based Assay (VCBA) model into a 3D spheroid cell model, we assumed that cells were arranged in a series of concentric layers within the sphere. Simplifying the spheroid with respect to number of cells in each layer, we formulate the process of chemical quasi-diffusion. The system was calibrated and tested using acetaminophen (APAP). Simulated predictions of the toxicity to APAP were validated with empirical data from in-vitro measurements using a 3D spheroid model. The results show that this first attempt of the VCBA model extension is promising. To this end the 3D VCBA model provides a complement to the current in-vitro procedures to refine experimental setups, to fill data gaps and help in interpretation of the in-vitro data for the purposes of risk assessment.

BEDNARCZYK Ewa;  LU Yanfei;  PAINI Alicia;  BATISTA LEITE Sofia;  VAN GRUNSVEN Leo;  WORTH Andrew;  WHELAN Maurice; 

2022-04-20

SAGE PUBLICATIONS LTD

JRC124609

0261-1929 (online),   

https://doi.org/10.1177/02611929221082200,    https://publications.jrc.ec.europa.eu/repository/handle/JRC124609,   

10.1177/02611929221082200 (online),