Chapters authored
Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals
The central nervous system (CNS) is a central pillar in safety pharmacology studies of new drugs. Characterization of serious adverse drug reactions to a new chemical entity involves extensive investigation using in vitro and in vivo models. However, primary culture of human neurons in vitro can be challenging, giving limited sample availability. Additionally, the inter-species differences between humans and current animal models impose a considerable obstacle to successfully predict the outcome of new drugs. New technologies also need to help address the 3Rs principles in animal research. Human pluripotent stem cells (hPSC) have the potential to change the current paradigm in pharmacological research. By using hPSCs and state-of-the-art differentiation protocols, researchers now have available an unlimited source of neural cells, able to mimic early and late stage of human CNS development. Moreover, hPSC-derived cells can be used at early stages of drug development, improving clinical predictability and reducing overall drug development costs. This chapter covers the advancements that resulted in hPSC-derived models intended to enable neurotoxicity assessment and drug screening. Finally, this chapter will also reveal the bottlenecks and the challenges to overcome of using hPSC as a predictive tool in research.
Part of the book: Neurotoxins