Human pluripotent stem cell (hPSC) models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms. In particular, hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo. In chimeric brains, human neural and immune cells can maintain human-specific features, undergo maturation, and functionally integrate into host brains, allowing scientists to study how human cells impact neural circuits and animal behaviors. The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease, elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels, and testing the efficacy of cell therapy interventions. Here, we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders, including disease modeling and cell therapy.

人类多能干细胞 (hPSC) 模型通过概括人类特有的疾病机制，为研究人类神经系统疾病提供了前所未有的机会。特别是，基于 hPSC 的人-动物脑嵌合体能够在体内研究人类细胞病理生理学。在嵌合大脑中，人类神经和免疫细胞可以保持人类特有的特征，经历成熟并在功能上整合到宿主大脑中，从而使科学家能够研究人类细胞如何影响神经回路和动物行为。新兴的人-动物脑嵌合体有望对人脑细胞及其在健康和疾病中的相互作用进行建模，阐明从分子和细胞到回路和行为水平的疾病机制，并测试细胞治疗干预的功效。在这里，我们讨论使用人-动物嵌合脑模型研究神经系统疾病（包括疾病建模和细胞治疗）的生成和应用的最新进展。