Optimization of a Human Induced Pluripotent Stem Cell-derived Sensory Neuron Model for the in Vitro Evaluation of Taxane-induced Neurotoxicity

Overview

Journal Sci Rep

Specialty Science

Date 2024 Aug 17

PMID 39154055

Authors

Erica L Cantor

Fei Shen

Guanglong Jiang

Santosh Philips

Bryan P Schneider

Affiliations

Soon will be listed here.

Abstract

Human induced pluripotent stem cell-derived sensory neuron (iPSC-dSN) models are a valuable resource for the study of neurotoxicity but are affected by poor replicability and reproducibility, often due to a lack of optimization. Here, we identify experimental factors related to culture conditions that substantially impact cellular drug response in vitro and determine optimal conditions for improved replicability and reproducibility. Treatment duration and cell seeding density were both found to be significant factors, while cell line differences also contributed to variation. A replicable dose-response in viability was demonstrated after 48-h exposure to docetaxel or paclitaxel. Additionally, a replicable dose-dependent reduction in neurite outgrowth was demonstrated, demonstrating the applicability of the model for the examination of additional phenotypes. Overall, we have established an optimized iPSC-dSN model for the study of taxane-induced neurotoxicity.

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