Abstract

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This study presents a novel 3D brain microphysiological system (BMPS) derived from human induced pluripotent stem cells (iPSCs). The model consists of mature neurons and glial cells that demonstrate key brain functions, including synaptogenesis, electrical signaling, and myelination. The BMPS shows reproducibility, functional complexity, and potential for studying diseases such as multiple sclerosis and for neurotoxicity screening.

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Key Learnings

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• Developed a reproducible, size-controlled 3D BMPS model using iPSCs.
• Demonstrated up to 40% axonal myelination, a rare achievement in vitro.
• Achieved neuron-glia interaction and synaptic activity measurable via MEA recordings.
• Enabled modeling of complex brain functions and pathologies in a human-relevant system.
• Offers a promising platform for drug testing, disease modeling, and neurotoxicity screening.

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Methods

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• iPSC Differentiation: Neural progenitor cells were derived from iPSCs and differentiated under gyratory shaking into brain-like spheroids.
• Characterization: Flow cytometry, qPCR, immunocytochemistry, and electron microscopy were used to assess cell types, maturation, and myelination.
• Electrophysiology: Microelectrode array (MEA) recordings captured spontaneous neuronal activity.
• Quantification: Myelination was quantified with automated image analysis and validated by electron microscopy.

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Conclusions

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This BMPS represents a significant advancement in modeling human brain physiology in vitro. With its demonstrated synaptic activity, electrical signaling, and robust myelination, it is a powerful tool for studying neurodevelopmental and neurodegenerative diseases, as well as evaluating neurotoxic effects of drugs and chemicals. Its reproducibility and compatibility with higher-throughput formats make it suitable for a range of translational applications.

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Reference

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Pamies D, Barrera P, Block K, et al. A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. ALTEX. 2017;34(3):362-376. doi:10.14573/altex.1609122