The stem-cell test-A novel in vitro assay for teratogenic potential.
The micromass test for teratogens (Flint and Orton, 1984) has undergone extensive validation for use in reproductive toxicology. A major drawback of this test is its use of primary cells derived from rat embryos. The stem-cell test is a novel assay for teratogenic potential which uses a propagated cell line. Mouse embryonic stem cells (ESC) are maintained in an undifferentiated state in the presence of leukaemia inhibitory factor (LIF). On removing LIF, the cells differentiate into an embryonic endoderm that is morphologically distinct from ESC. Colonies of ESC are maintained from which cells can be harvested daily, and these cells, when washed free of LIF, form a population of differentiating cells on which the effects of chemicals can be tested. The conditions under which differentiating ESC can be substituted for rat primary embryonic cells in a micromass test protocol have been determined, and the effects of 25 compounds investigated in a blind trial. The stem-cell test predicted the teratogenicity of these compounds with a similar sensitivity and specificity to the micromass test, with the advantage that the test uses a propagated cell line; there is no use of animals.
Newall
D R
DR
Genetic and Reproductive Toxicology, Glaxo Group Research Ltd, Ware, Herts. SG12 ODP, UK.
Beedles
K E
KE