Frontiers in pluripotent stem cells research and therapeutic potentials Chapter titile: Stem Cell Technologies and their Application in Modern Toxicology- Current State of the Art

Chemicals produced by various industrial sectors such as drugs, cosmetics, agrochemicals and industrial chemicals are obliged to undergo a rigorous safety assessment before their entry into the market. Today the standard information requirements providing the necessary details on the toxicity of the individual compounds are mainly derived from tests performed in laboratory animals. The principal drawbacks of such in vivo tests are their length, cost, the remaining uncertainty for humans and the associated ethical concerns. Therefore there is a strong desire of toxicologists to compile the increasing scientific knowledge as well as emerging technologies and methodologies in a framework that drives safety assessments towards a mechanistic understanding of chemically induced toxicity. An integer part of such modern toxicology are human based in vitro tests that are designed to allow a high throughput of substances and to specifically elucidate relevant toxicological mechanisms. The most promising source of human cells are stem cells since these cells can be propagated in vitro indefinitely, provide all toxicologically relevant target cells and they do not exhibit unwanted characteristics of cell lines with a carcinogenic origin. However, the establishment of in vitro toxicity tests based on human pluripotent stem cells is challenging since differentiation protocols are often unstable, the cell cultures are not pure and the differentiation is not leading to fully matured cells that are toxicologically relevant. A first step in test development to tackle these challenges is the establishment of high quality standards which will support the reproducibility of test results within a laboratory set up but also between laboratories. In the last years, many progress have been made to develop test systems particularly in areas of toxicity where human cellular models are not available but strong interspecies variations exists such as developmental toxicity, cardiotoxicity and hepatotoxicity. However, no pluripotent stem cell- based toxicity test has been formally validated yet.JRC.I.5-Systems Toxicolog