Levy Rebecca J, Paşca Sergiu P
Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.
Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute & Bio-X, Stanford University, Stanford, California, USA; email:
Annu Rev Neurosci. 2025 Jul;48(1):363-379. doi: 10.1146/annurev-neuro-112723-023232. Epub 2025 Apr 18.
To understand the pathophysiology of and develop effective therapeutics for brain disorders, some of which may involve uniquely human features of the nervous system, scalable human models of neural cell diversity and circuit formation are essential. The discovery of cell reprogramming and the development of approaches for generating stem cell-derived neurons and glial cells in 3D preparations known as neural organoids and assembloids, both in vitro and following transplantation in vivo, provide new opportunities to tackle these challenges. Here, we outline strengths and limitations of currently available human experimental models as applied to neurological and psychiatric disorders for both environmental and genetic risk factors, and we discuss how these new tools hold promise for accelerating the development of therapeutics.
为了理解脑部疾病的病理生理学并开发有效的治疗方法,其中一些疾病可能涉及神经系统独特的人类特征,可扩展的人类神经细胞多样性和神经回路形成模型至关重要。细胞重编程的发现以及在体外和体内移植后在称为神经类器官和类组装体的3D制剂中生成干细胞衍生的神经元和神经胶质细胞的方法的发展,为应对这些挑战提供了新机会。在这里,我们概述了当前可用的人类实验模型在应用于神经和精神疾病的环境和遗传风险因素方面的优势和局限性,并讨论了这些新工具如何有望加速治疗方法的开发。