Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their research. The search strategy was developed with assistance from a clinical librarian and conducted in MEDLINE (PubMed) and Embase (Ovid) on September 26, 2023. Twenty-six peer-reviewed experimental studies presenting original data about human reprogrammed nonmotor neuron cell culture systems and relevant market available chemotherapeutics drugs were included. Virtually, all recent reports modeled CIPN using nociceptive dorsal root ganglion neurons. Drugs known to cause the highest incidence of CIPN were most used. Furthermore, treatment effects were almost exclusively validated by the acute effects of chemotherapeutics on neurite dynamics and cytotoxicity parameters, enabling the extrapolation of the half-maximal inhibitory concentration for the 4 most used chemotherapeutics. Overall, substantial heterogeneity was observed in the way studies applied chemotherapy and reported their findings. We therefore propose 6 suggestions to improve the clinical relevance and appropriateness of human cellular reprogramming-derived CIPN models.

中文翻译：

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由人类诱导多能干细胞和直接转化细胞构建的化疗诱导的周围神经病变模型：系统评价。

人类细胞重编程的发展现在允许生成用于体外疾病模型的人类神经元。该技术后来被用于化疗引起的周围神经病变 (CIPN) 研究，从而描述了许多由人类神经元构建的 CIPN 模型。本系统综述为旨在将人类体外 CIPN 模型纳入其研究的潜在研究人员提供了对可用模型及其方法学考虑因素（即使用的细胞类型和来源、CIPN 诱导策略和验证方法）的批判性分析。该检索策略是在临床图书馆员的协助下制定的，并于 2023 年 9 月 26 日在 MEDLINE (PubMed) 和 Embase (Ovid) 上进行。26 项同行评审的实验研究提供了有关人类重编程非运动神经元细胞培养系统和相关的原始数据市场上可用的化疗药物也包括在内。事实上，所有最近的报告都使用伤害性背根神经节神经元来模拟 CIPN。已知导致 CI​​PN 发生率最高的药物使用最多。此外，治疗效果几乎完全通过化疗药物对神经突动力学和细胞毒性参数的急性影响来验证，从而能够外推 4 种最常用化疗药物的半最大抑制浓度。总体而言，研究应用化疗和报告研究结果的方式存在显着的异质性。因此，我们提出 6 条建议，以提高人类细胞重编程衍生的 CIPN 模型的临床相关性和适当性。