Hematology/Oncology Division, Indiana University School of Medicine, Indianapolis, IN, USA.
Medical and Molecular Genetics Division, Indiana University School of Medicine, Indianapolis, IN, USA.
Sci Rep. 2024 Aug 17;14(1):19075. doi: 10.1038/s41598-024-69280-z.
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.
人诱导多能干细胞衍生感觉神经元（iPSC-dSN）模型是研究神经毒性的有价值的资源，但由于缺乏优化，其可重复性和再现性往往受到影响。在这里，我们确定了与培养条件相关的实验因素，这些因素会极大地影响细胞的体外药物反应，并确定了提高可重复性和再现性的最佳条件。处理时间和细胞接种密度均被发现是重要因素，而细胞系差异也导致了变化。在紫杉醇或多西紫杉醇 48 小时暴露后，可证明细胞活力具有可复制的剂量反应。此外，还证明了神经突生长的可复制的剂量依赖性减少，表明该模型适用于检查其他表型。总的来说，我们已经建立了一个优化的 iPSC-dSN 模型，用于研究紫杉醇诱导的神经毒性。
