Paclitaxel Dose in iPSC-Generated Sensory Neurons for Ex Vivo Modeling of Taxane-Induced Peripheral Neuropathy

Purpose: To establish an ex vivo model of paclitaxel induced peripheral neuropathy that can be translated clinically using induced human neurons. Experimental Design: Human induced pluripotent stem cells (iPSCs) will be differentiated into mature sensory neurons. After reaching maturation, neurons will be treated with varying doses (0nM, 25nM, 50nM, and 75nM) of paclitaxel to identify the ideal concentration to model paclitaxel-induced peripheral neuropathy ex vivo. Various phenotypic changes will be assessed including changes in morphology, viability, number of dendritic processes, and sensory marker expression patterns. Results: Paclitaxel dosing at 25 nM allows for a 23% reduction in processes length (p=0.04), 50 nM and 75 nM allow for a 51% and 59% reduction in process length (respectively, p\u3c0.0001) while maintaining viable neurons. Conclusion: The administration of 50 nM of paclitaxel to iPSC derived neurons presents an ex vivo method to model paclitaxel induced neuropathy in patients that receive 80 mg/m2 of weekly paclitaxel