Peripheral Neuropathy Research Group, Department of Biomedical Sciences, University of Antwerp, 2610, Antwerp, Belgium.
Laboratory of Neuromuscular Pathology, Institute Born Bunge, 2610, Antwerp, Belgium.
Exp Mol Med. 2024 Jun;56(6):1348-1364. doi: 10.1038/s12276-024-01250-x. Epub 2024 Jun 3.
Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids.
遗传性周围神经病（IPN）是一组与各种基因的突变相关的疾病，这些基因在外周神经的发育和功能中起着重要作用。在过去的 10 年中，通过细胞生物学研究和转基因果蝇和啮齿动物模型，在确定轴突和髓鞘变性的分子疾病机制方面取得了重大进展，这为有前途的治疗策略的发展提供了便利。然而，迄今为止还没有出现临床治疗方法。这种缺乏治疗方法突出表明，迫切需要更具生物学和临床相关性的模型来重现 IPN。对于神经发育和神经退行性疾病，患者特异性诱导多能干细胞（iPSC）是疾病建模和临床前研究的特别强大平台。在这篇综述中，我们提供了不同体外人类细胞 IPN 模型的最新更新，包括传统的二维单核培养 iPSC 衍生物，以及使用微流控芯片、类器官和组装体的更复杂的基于人类 iPSC 的系统的最新进展。
