![]() ![]() In particular, most current models are static and do not model the dynamics of in vivo tissue perfusion and mechanical stress forces. However, these models do not fully represent the complexity of many in vivo tissues, often lacking relevant cell types and required growth factors, and are not subject to long-distance signalling from other organs, the immune system, the endocrine system or the microbiome. In most cases, cells are grown embedded in extracellular matrices to form organoids or spheroid-like structures. Relevant differences in cellular behaviour between 2D and 3D cultures have been characterized in several prominent studies, reporting the greater physiological relevance of 3D models compared with similar 2D models. There have been substantial developments in the field of cell-based screening during the last decade, such as the emergence of stem cell technologies, microtissues, organoid models and organ-on-a-chip platforms. Specifically, scientific community representatives highlight the lack of validated methodologies and software tools that enable robust quantitative analysis of the vast number of newer 3D cellular models. Prominent cellular high-content screening (HCS) and bioimage informatics societies are therefore calling for further debate to discuss the value of these emerging 3D model systems in an effort to establish more transparent and standardized guidelines in the field. However, there is a lack of conclusive evidence that such models accurately recapitulate in vivo tissue physiology and disease pathophysiology, and thereby provide sufficiently quantitative and reproducible data to replace current models and improve the clinical success rates of drug candidates. A rapidly expanding offering of commercially available in vitro technologies for high-throughput 3D cell-based disease models, combined with advances in material sciences, are enabling widespread application and adoption of these models across academic and industrial research groups. There is intense excitement in the scientific community about 3D cellular model systems because they promise to resemble and recapitulate the in vivo tissue environment more faithfully than 2D systems 1. ![]()
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