Embryonic stem cells as an in vitro model for mutagenicity, cytotoxicity and embryotoxicity studies: present state and future prospects

Primary cultures or established cell lines of vertebrates are commonly used to analyse the mutagenic, embryotoxic or teratogenic potential of environm ental factors, drugs and xenobiotics in vitro. However, these cellular syst ems do not include developmental processes from early embryonic stages up t o terminally differentiated cell types. An alternative approach has been of fered by permanent lines of pluripotent stein cells of embryonic origin, su ch as embryonic carcinoma (EC), embryonic stem (ES) and embryonic germ (EG) cells. The undifferentiated stem cell lines are characterized by nearly un limited self-renewal capacity and have been shown to differentiate in vitro into cells of all three primary germ layers. Pluripotent embryonic stem ce ll lines recapitulate cellular developmental processes and gene expression patterns of early embryogenesis during in vitro differentiation, data which are summarized in this review. In addition, recent studies are presented w hich investigated mutagenic, cytotoxic and embryotoxic effects of chemical substances using in vitro systems of pluripotent embryonic stein cells. Fur thermore, an outlook is given on future molecular technologies using embryo nic stem cells in developmental toxicology and embryotoxicology. (C) 2001 E lsevier Science Ltd. All rights reserved.