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Human stem cell models for neurotoxicity screening

3D human cell microscope background
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Jun 12 2017

JRC scientists have shown human induced pluripotent stem cell (hiPSC) to be a promising in vitro model for neurotoxicity testing. These stem cell-based systems offer an innovative human-relevant alternative to traditional animal tests that can improve the efficacy of drug discovery and support safety assessment.

Current toxicity screening is focused on strategies to reduce animal testing by implementing human cell-based models. The JRC's EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) promotes the development and dissemination of alternative methods, such as the use of in vitro test systems based on human induced pluripotent stem cell (hiPSC) to enable mechanistic understanding of chemically-induced adverse effects.

Neuronal models derived from hiPSC can be used to assess the activation of the Nrf2 signaling pathway, a biomarker of oxidative stress. Oxidative stress is an important hallmark of various neurodegenerative diseases, including Parkinson's disease (PD).

Treatment with rotenone, an inhibitor of mitochondrial respiration, induced the activation of Nrf2 signaling, together with an increase of astroglial cells and a decrease of dopaminergic neurons cells, the most vulnerable neuronal cell-type in PD.

These data suggest that neuronal/glial cell cultures derived from hiPSCs show promise as a model for in vitro neurotoxicity testing of chemicals that induce oxidative stress and trigger Nrf2 pathway activation.

Read more in: Zagoura D, Canovas-Jorda D, Pistollato F, Bremer-Hoffmann S, Bal-Price A., Evaluation of the rotenone-induced activation of the Nrf2 pathway in a neuronal model derived from human induced pluripotent stem cells. Neurochem Int. 2016 Sep 9. pii: S0197-0186(16)30284-4. doi: 10.1016/j.neuint.2016.09.004