State-of-the-Art of Cell Cultures in Drug Validation and Toxicity Assessment

Dear Colleagues,

Chemical risk assessment has relied on animal testing for decades. The system's overall performance, sustainability, relevance and ethics are being questioned by society and the scientific community, revisiting the 'gold standard' rodent tests, for instance, in repeated-dose toxicity, carcinogenicity studies and potential adverse effects of chemicals which can be combined to form mixtures. These issues necessitate a paradigm shift towards a new toxicity testing system that evaluates biologically significant perturbations in key toxicity pathways. To achieve these goals, new prediction models should consider novel intelligent and more efficient safety assessments based on in vitro testing in combination with computational modelling. Indeed, several up-to-date scientific tools used for risk assessment are continuously enhancing through the development of new methodological approaches (NAMs) based on complex in vitro models, omic sciences, biological analysis of high-performance screening and quantitative structure–activity relationships (QSAR). The challenge of using NAMs to assess hazards and risks is aligned with the One Health approach.

 A good in vitro model should be as close as possible to in vivo conditions to better reproduce the response of the organism. Therefore, translation into 3D-reconstructed model tissues from primary human cells enables microphysiological disease modelling, drug discovery and toxicity testing, as they are increasingly integrating advanced human cell culture systems and techniques, which include induced pluripotent stem cells (iPSC), 3D cultures and organoids (from healthy or cancer cells), co-culture systems, microfluidics and multiorgan chips.

Moreover, these innovative models can mimic the key events that underlie the AOP (adverse outcoming pathway) concept, a significant step forward towards the goal of full animal replacement in toxicology.  

This Special Issue is dedicated to collating information on state-of-the-art cell culture models and techniques. We will highlight the current knowledge and future potential of cell cultures, spotlighting a unique tool to test the effect of new target drugs and study in vitro toxicity assessment, which will provide novel insights into the field of cellular biology. Both original research articles and reviews about experimental cytology are welcome. We look forward to receiving your contributions.

Dr. Anna Bassi
Dr. Stefania Vernazza
Guest Editors

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• human in vitro models
• toxicity testing
• drug development
• mandatory requirements
• regulatory approval
• standardization
• validation

Title: Advances in cellular and molecular mechanisms using 3D in vitro cell cultures: brief focus on breast cancer, endometriosis, liver, and infections
Authors: Nora Bloise; Marialaura Giannaccari; Giuseppe Guagliano; Emanuela Peluso; Elisa Restivo; Silvia Strada; Cristina Volpini; Paola Petrini; Livia Visai
Affiliation: Department of Molecular Medicine, Centre for Health Technologies (CHT), INSTM, UdR of Pavia, University of Pavia, UOR6 Nanotechnology Lab., Department of Prevention and Rehabilitation in Occupational Medicine and Specialty Medicine, Istituti Clinici Scientifici Maugeri IRCCS, Interuniversity Center for the promotion of the 3Rs principles in teaching and research (Centro 3R), University of Pavia Unit, Italy
Abstract: Over the last decade, the development of 3D models has increased rapidly to help unravel the fundamental and essential cellular mechanisms by which cells communicate with each other, assemble into tissues and organs, and respond to biochemical and biophysical stimuli under both physiological and pathological conditions. Here is a brief overview of the most recent updates on the significant contribution of 3D cell culture in advancing our understanding of cellular and molecular mechanisms, considering the case of breast cancer, endometriosis, liver microenvironment, and infections. The interested reader will also find concluding remarks on the challenges and prospects of using 3D cell cultures for discovering cellular and molecular mechanisms in the research areas covered in this review.