Stem cell-based in vitro models as alternative methods for toxicity and efficacy tests in animals

Regarding toxicity and efficacy tests of pharmacological and chemical substances (REACH legislation in Europe), there is a strong need to develop alternative methods for animal in vivo studies, in particular for human in vitro models. Here we present results from early phases of projects exploring the potential of embryonic stem cell models, with a special emphasis on embryo toxicity and neuronal stress. We have been able to demonstrate key functional read-outs of neural hESC models, in addition to representing mechanistic aspects which are characteristic for ischemia or excitotoxicity. There is agreement that these mechanisms underlie a variety of human neurodegenerative diseases. We discuss the possibilities to develop more precise endpoints on the molecular level and present an example of a protein biomarker signature emerging from a European FP6 project about embryo toxicity (www.reprotect.eu), employing murine and human embryonic stem cell models.