Embryonic stem cells for drug toxicity studies An EU-initiative used human embryonic stem cells to develop hepatic models for drug toxicity testing. Health © Thinkstock Adverse drug side effects constitute a major cause of mortality, while pharmacokinetic problems cause nearly 40 % of new drugs to fail in clinical trials. The pharmaceutical industry currently relies on the use of fractionated human tissue and animal models to study the metabolic and pharmacokinetic properties of new drugs. However, these have poor predictive power necessitating the development of reliable tools to predict possible toxicity of new compounds before they are passed on to the clinical phase. The main objective of the 'Reducing animal experimentation in pre-clinical predictive drug testing by human hepatic in vitro models derived from embryonic stem cells' (Vitrocellomics) project was to establish cell lines derived from human embryonic stem cells (hESC) that could be used in the drug discovery process to replace animal experimentation. The project combined clinical, bioengineering and pharmaceutical expertise to establish and refine protocols used for differentiation of hESC lines to mature liver cells. These cells closely resembled human liver in terms of functionality and clearance of drugs. When tested in toxicity and drug metabolism assays, these hESC-derived liver cells revealed superior predictability potential compared to current models. The project also incorporated the method of optical sensing of oxygen consumption (respiration assay) in their toxicity test platform for in vitro screening of new drugs. The Vitrocellomics-developed hESC system reduces the use of animal experimentation in the drug discovery and development processes. Finally, it offers a significant enhancement to prediction of human drug metabolism in terms of efficacy, safety and quality.
