The development and optimization of a 3D spheroid model for respiratory toxicity study

Traditionally, chemical toxicity testing is largely based on in vivo experiments using laboratory animals. The 3R concept (Replacement, Reduction, and Refinement) formulated by Russel and Burch (1959), together with regulatory initiatives (e.g. by the European Union) resulted in a shift towards the use of alternative methods. In more recent years, there has been an increase in the development of new three-dimensional (3D) culture models, and the techniques used to develop these models (e.g. spheroid cultures, microcarrier cultures, co-culture models, ...), owing to their ability to accurately mimic human physiology and pathology. 3D cell cultures are believed to show more accurate cell-cell interactions, morphology, responses to stimuli, and gene expression compared to the commonly used two-dimensional (2D) cultures. These 3D models could herald a new chapter in a multitude of fields including the toxicity assessment of compounds and particles. Nevertheless, 3D in vitro models for lung tissue specifically are quite rare and/or often not well characterized and optimized. Previously, in our lab, we developed a new 3D in vitro lung model for respiratory toxicity studies and optimized the model to be used for Next Generation Risk Assessment (NGRA). Further research will focus on the further optimization and complexifying the 3D lung model (e.g. co-culturing) as well as implementing the model for NGRA.