Pluripotent stem cells are able to proliferate indefinitely and differentiate in vitro into various cell types. However, in most cases in vitro differentiation of the pluripotent stem cells is asynchronous and incomplete, and the residual undifferentiated cells can initiate
teratoma development after
transplantation into recipients. These features of the pluripotent stem cells are the major issue for development of safe
cell therapy technologies based on pluripotent stem cells. Considering significant resemblance of growth rates of pluripotent stem and
cancer cells we investigated antiproliferative and cytotoxic effects of different type
cytostatics (
mitomycin C,
etoposide,
vinblastine and
cycloheximide) on the undifferentiated and differentiating mouse embryonic stem cells, embryonic germ cells, blastocyst and on mouse embryonal
teratocarcinoma cells and mouse embryonic fibroblasts. The findings showed that all
cytostatics used induced both antiproliferative effects and acute toxic processes in undifferentiated pluripotent stem cells and embryonal
teratocarcinoma cells whereas these effects were less in differentiating embryonic stem cells and embryonic fibroblast. Moreover, the trophoblast cells of mouse blastocysts were less sensitive to damaging effects of
cytostatics than inner cell mass cells. The examination of deferred effects ofcytostatics revealed that the effects ofmitomycin C,
etoposide and
vinblastine, but not
cycloheximide, were irreversible because survived cells were not able to proliferate. Nevertheless, the numbers of embryonic fibroblasts exposed to
etoposide or
vinblastine remained unchanged while vast majority of undifferentiated pluripotent cells treated underwent apoptosis. Thus, diverse effects of
etoposide and
vinblastine on the undifferentiated pluripotent stem cells and differentiated embryonic cells allow us to consider these
cytostatics and their analogs as
drug-candidates for selective elimination of the residual undifferentiated pluripotent stem cells from population of differentiating cells. These findings demonstrate for the first time the possibility of selective elimination of undifferentiated pluripotent stem cells using
cytostatic drugs approved for clinic practice. However, to improve effectiveness and safety of this approach and to prevent mutagenic, carcinogenic and teratogenic effects on undifferentiated pluripotent stem cells and their differentiated cell derivatives large-scale studies ofcytostatic effects using different experimental design and active doses must be performed.