The PluriLum assay: A novel stem cell-based assay for testing of chemicals’ embryotoxic effects
Due to scientific, economic, and ethical conditions, there is a great need to develop novel human and physiologically relevant methods for testing chemicals for developmental toxicity. This area accounts for a large proportion of the experimental animals used for testing in connection with risk assessment of industrial chemicals. We have developed a human-induced pluripotent stem cell-based test method, called PluriLum, which has the potential to become part of a future testing strategy for developmental toxicity.
The method builds on 3D cultures of aggregated stem cells, so-called ‘embryoid bodies’, which mimic the very early human fetus formed 4 days after conception of the fetus. By differentiating these embryoid bodies into beating cardiac cells we mimic the earliest developing organ in the body. We have genetically modified the stem cells so that activity of the early heart differentiation marker NKX2.5 is easily detected using a luminescence reporter. We want to delineate the scope of the PluriLum assay by testing a wide panel of substances and compare the effects with those seen in other experimental models and to dig into the mechanisms of actions for a few selected compounds. The project will further shed light on the potential of the PluriLum assay in a future test strategy for embryotoxicity of chemicals.
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