Healthy stem cells in toxicological research and drug screening

In vitro toxicology protocols typically use cell lines that were isolated from already transformed tissues or that were immortalized by various techniques, such as overexpression of oncogenes. In the dish, a cell clone with high proliferative activity becomes the only or most numerous cell type, losing the natural heterogeneity of the original tissue and presenting a transformed phenotype/molecular identity. More closely resembling the in vivo situation, primary cells are an option, but these cells quickly undergo senescence, and isolation and variety of primary cultures hampers their broad use in cell biology and in vitro toxicology.

The combination of autonomous self-renewing capacities and non-altered phenotypic and molecular properties is found in stem cells, which renew/regenerate various tissues in the animal body. Somatic stem cells typically replace specific kinds of progenitor cells for the given tissue, so the molecular programs are already determined to some extent. Alternatively, iPSCs (induced-pluripotent stem cells), generated from any tissue into embryonic stem cells, have been successfully reprogrammed and differentiated into most other cell types for molecular analyses, exploiting also patient-derived genomic
features into in vitro analyses.

This research topic aims to provide an overview of stem cells and their advantages in applied toxicology, extending to drug screening or closely related applications. The first aim is to emphasize the advantages and possible disadvantages, as well as current technological limitations, of stem cells and of cell lines derived thereof in the research areas mentioned above. Additionally, the integration of the “adverse outcome pathway” perspective into in vitro research and the related opportunities to replace animal testing shall be highlighted. A specific topic invited is also the molecular mechanisms identifying transforming capacities in healthy stem cells towards carcinogenesis or cancer stem cells. Lastly, we welcome articles that use stem cells or improve their isolation protocols to screen or develop screening protocols with the aim of understanding the foundations of molecular pathways in stem cells or to apply targeted methods in toxicology and drug screening to those.

Keywords: Healthy stem cells, induced stem cells, toxicology, 3R, AOP, mechanisms of pluripotency, carcinogenesis, cancer stem cells

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