Majumder Joydeb, Murphy William L
Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA.
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Curr Res Toxicol. 2025 Jul 11;9:100249. doi: 10.1016/j.crtox.2025.100249. eCollection 2025.
Neurotoxicity studies often depend on traditional cell-based monoculture assays and animal models, which have a number of limitations. In particular, the existing models either lack the appropriate physiological context, do not include a functional blood-brain barrier, or include cells from non-human species. The recent emergence of organoids derived from human pluripotent stem cells has provided new opportunities to understand disease etiology, discover drugs, evaluate efficacy, and evaluate toxicity in physiologically relevant contexts. Organoids comprised of organ specific precursor cells can potentially overcome the limitations of the traditional 2D cell culture and animal models in neurotoxicology studies. Here, we provide a review of recent developments of human neural organoids, and summarize their applications in neurotoxicity testing. We also discuss their several limitations, and provide a future perspective on their widespread use in neurotoxicity studies.
神经毒性研究通常依赖于传统的基于细胞的单培养分析方法和动物模型,而这些方法存在诸多局限性。特别是,现有的模型要么缺乏合适的生理背景,不具备功能性血脑屏障,要么包含来自非人类物种的细胞。最近由人类多能干细胞衍生而来的类器官的出现,为在生理相关背景下理解疾病病因、发现药物、评估疗效和评估毒性提供了新的机会。由器官特异性前体细胞组成的类器官有可能克服传统二维细胞培养和动物模型在神经毒理学研究中的局限性。在此,我们综述了人类神经类器官的最新进展,并总结了它们在神经毒性测试中的应用。我们还讨论了它们的一些局限性,并对其在神经毒性研究中的广泛应用提供了未来展望。