"The future of in vitro toxicology"

Abstract

In 1959 Russell and Burch stated that "Mammalian tissue cultures have become one of the most important replacement techniques". Although they would likely be disappointed at the slow progress towards the 3Rs, I am sure they would be amazed and excited about the advances made. For example, omic technologies now provide an unbiased holistic view of cellular events and help the development of new mechanistic biomarker sets. New techniques to immortalise cells, such as telomerase overexpression, allow us to create human cell lines without introducing viral oncogenes and thereby provide a source of cells with normal phenotypes. In addition, the truly ground-breaking discovery of inducible pluripotent stem cells allows the possibility of generating target tissues from any individual. There has also been great advances in material science and bio-engineering, creating exciting new microfluidic devices which are well placed for the development of in vitro multi-organ systems. All of these advances have allowed us to better understand the mechanisms of how cells deal with chemical induced cellular perturbations. Utilising this knowledge and these tools, together with biokinetics we can create strategies that will be useful for regulatory purposes. Only in such an integrated interdisciplinary way will we ensure that human in vitro systems become critical toxicological tools, eventually replacing animal models altogether.

Keywords: 3R; Omics; Stem cells; iPSC.