Metabolically competent stem cell systems: novel means to implement 3Rs in better drug safety assessment
Aim
Developmental toxicology studies are carried out in animals to detect whether medicines are safe to be taken by pregnant women. Effects on development of the embryo and fetus are measured during these tests. Approximately 200,000 animals are used each year in Europe for this purpose. A test involving stem cells from mice embryos is currently used to answer some questions, but is not completely reliable because it cannot detect many drugs that have a smaller, but still significant toxic effect. Importantly, these tests do not recreate how the drugs would be metabolised and whether this would have any effect. The aim of this research is to 'humanise' this test to make it more predictive.
Method
The mouse embryonal stem cell test will be humanised by incorporating human drug metabolism by the addition of enzymes that are found in the liver. The project will also be employing stem cells from the human umbilical cord, which have the potential to be turned into different types of cell from the human body, to see how effective they are for testing reproductive toxicology.
Implications for the 3Rs
If the test can be made more relevant then this non-animal test has the potential to replace the use of more than 30,000 animals per year in Europe for embryotoxicity tests in the pharmaceutical industry.
