An iPSC-derived neuroinflammation/neurotoxicity in vitro model of neurons and glial cells

Neuroinflammation occurs in most, if not all, neurodegenerative and inflammatory diseases. Mono in vitro cultures of astrocytes and microglia are powerful tools to study specific molecular pathways involved in neuroinflammation. However, more complex neuronal in vitro models are required to capture the effects of cellular communication on neuroinflammation and neurodegeneration in a human-based model which reduces animal testing in the early stages of drug discovery.

Charles River Laboratories successfully implemented a multicellular co-culture model using iPSC-derived glutamatergic neurons, oligodendrocyte-like cells, astrocytes and microglia that can be used in the early stages of drug discovery. Inducing acute neuroinflammation with the tested triggers caused neuronal and oligodendrocyte damage and microglia activation and clustering, especially with a high concentration of Aβ monomers. In addition, nigericin induced excessive toxicity. Next to high imaging, Nf-L detection on culture supernatant was used as a measure for neurotoxicity and degeneration upon treatment with the different triggers.