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Establishment of human iPSC-derived models in neurobiology and neurodegeneration

The development of physiological relevant models for neurodegenerative diseases remains a challenge, with an unmet need in translatable human-based platforms. With the emergence of iPSC technology, it is now possible to generate brain-derived cell types, namely neurons, astrocytes and microglia, that are key players in multiple disease pathogenesis.

Cortical neurons derived from human iPSCs were recently developed by Ncardia that are post mitotic, cortical layer committed and display branching phenotype. These neurons also exhibit spontaneous activity on MEA, presenting firing and bursting properties as early as day 7 and evolve into more complex structured patterns of activity.

To better understand the role of neuroinflammation in early stages of neuropathology, Ncardia developed a new protocol for the generation of microglia, which is based on the differentiation steps that occur during human development. The monocyte precursors exhibit common identity markers such as CD45+/CD11b+/CD14+ and are generated in high purity and viability, which makes them a reliable source to produce microglia in a later stage of development. The resulting microglia cells have typical dynamic behaviour and dual morphology (ramified/ameboid) and express the microglia-specific marker Iba1 when in co-culture with our cortical neurons.

The co-culture of cortical neurons, microglia and Ncyte Astrocytes present a more translatable and versatile system, incorporating both neuronal and support glial cells generated from the same donor. High content imaging techniques coupled with long-term functional assays developed at Ncardia provide insight into neurobiology and neuropathology by evaluating parameters as cell health, morphology and function.


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