Abstract

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Background & Purpose:

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High-throughput screening (HTS) for neurotoxicity has lagged due to the absence of physiologically relevant human neuronal cell models. This study addresses that gap by developing and evaluating a co-culture system of human iPSC-derived sensory neurons (hSNs) and primary human Schwann cells (hSCs) to improve the prediction of chemotherapeutic drug safety.

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Methods:

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The study compared 2D monocultures and co-cultures using Paclitaxel and Oxaliplatin. Key metrics included neurite length, total processes, total branches, and cell counts. Multielectrode arrays (MEA) were also used to assess neuronal firing rates.

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Results:

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• Co-cultures demonstrated higher effective concentration (EC50) values than monocultures, indicating greater resilience.
• Paclitaxel exhibited greater toxicity on Schwann cells than neurons, while Oxaliplatin showed no neurotoxicity in monocultures but induced toxicity in co-cultures.
• Co-cultures demonstrated higher spontaneous firing rates compared to monocultures.
• Neurons-only conditions were slower to reach electrical activity, especially in low-density conditions.

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Conclusion:

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This study highlights the value of co-culture systems in improving the accuracy of chemotherapeutic neurotoxicity assessments. The system effectively models Schwann cell involvement and enables robust screening for drug-induced neurotoxicity.