Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China; Gansu University of traditional Chinese medicine, Lanzhou 730030, PR China.
Exp Neurol. 2024 Sep;379:114848. doi: 10.1016/j.expneurol.2024.114848. Epub 2024 Jun 8.
The establishment of reliable human brain models is pivotal for elucidating specific disease mechanisms and facilitating the discovery of novel therapeutic strategies for human brain disorders. Human induced pluripotent stem cell (iPSC) exhibit remarkable self-renewal capabilities and can differentiate into specialized cell types. This makes them a valuable cell source for xenogeneic or allogeneic transplantation. Human-mouse chimeric brain models constructed from iPSC-derived brain cells have emerged as valuable tools for modeling human brain diseases and exploring potential therapeutic strategies for brain disorders. Moreover, the integration and functionality of grafted stem cells has been effectively assessed using these models. Therefore, this review provides a comprehensive overview of recent progress in differentiating human iPSC into various highly specialized types of brain cells. This review evaluates the characteristics and functions of the human-mouse chimeric brain model. We highlight its potential roles in brain function and its ability to reconstruct neural circuitry in vivo. Additionally, we elucidate factors that influence the integration and differentiation of human iPSC-derived brain cells in vivo. This review further sought to provide suitable research models for cell transplantation therapy. These research models provide new insights into neuropsychiatric disorders, infectious diseases, and brain injuries, thereby advancing related clinical and academic research.
建立可靠的人类大脑模型对于阐明特定疾病机制和促进发现人类大脑疾病的新治疗策略至关重要。人类诱导多能干细胞（iPSC）表现出显著的自我更新能力，并能分化为特化的细胞类型。这使得它们成为异种或同种异体移植的有价值的细胞来源。由 iPSC 衍生的脑细胞构建的人-鼠嵌合脑模型已成为模拟人类大脑疾病和探索脑疾病潜在治疗策略的有价值的工具。此外，这些模型有效地评估了移植干细胞的整合和功能。因此，本综述全面概述了将人类 iPSC 分化为各种高度特化的脑细胞类型的最新进展。本综述评估了人-鼠嵌合脑模型的特征和功能。我们强调了它在脑功能中的潜在作用及其在体内重建神经回路的能力。此外，我们阐明了影响体内人 iPSC 衍生脑细胞整合和分化的因素。本综述还旨在为细胞移植治疗提供合适的研究模型。这些研究模型为神经精神疾病、传染病和脑损伤提供了新的见解，从而推进了相关的临床和学术研究。
