Human-mouse chimeric brain models constructed from iPSC-derived brain cells: Applications and challenges

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-06-08 DOI:10.1016/j.expneurol.2024.114848

Ya Zhao , Ke Liu , Yinghua Wang , Yifan Ma , Wenwen Guo , Changhong Shi

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引用次数: 0

Abstract

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.

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由 iPSC 衍生脑细胞构建的人鼠嵌合脑模型：应用与挑战。

建立可靠的人脑模型对于阐明特定的疾病机制和发现治疗人脑疾病的新策略至关重要。人类诱导多能干细胞（iPSC）具有显著的自我更新能力，并能分化成特异的细胞类型。这使它们成为异种或异体移植的重要细胞来源。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脑部疾病和探索脑部疾病潜在治疗策略的重要工具。此外，这些模型还有效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分化成各种高度特化的脑细胞的最新进展。本综述评估了人鼠嵌合脑模型的特点和功能。我们强调了它在大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，我们还阐明了影响人 iPSC 衍生脑细胞在体内整合和分化的因素。本综述进一步寻求为细胞移植疗法提供合适的研究模型。这些研究模型为神经精神疾病、传染性疾病和脑损伤提供了新的见解，从而推动了相关的临床和学术研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.