Abstract

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Background & Purpose

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The study aimed to develop a 3D in vitro Nerve-On-A-Chip model using induced pluripotent stem cells (iPSCs) derived from healthy individuals and those with SOD1 mutations. The goal was to create a system that models motor neuron diseases and facilitates preclinical neurotoxicity testing.

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Methods

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The team utilized microengineered hydrogel scaffolding to control and confine 3D axon growth, simulating nerve fiber tracts. Key evaluation metrics included robust nerve growth, fasciculation, and glial interactions.

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Results

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The model successfully demonstrated robust neurite outgrowth (~5mm) in both healthy and SOD1 motor neurons. Histological examination revealed ultrastructural differences between the two cell types. Healthy motor neurons showed electrical activity through extracellular recording of compound action potentials.

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Conclusion

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This innovative 3D Human-Motor-Nerve-On-A-Chip effectively models motor neuron diseases, showing potential for robust in vitro testing in neurotoxicity studies and pharmacological screening.