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用于研究帕金森病发病机制和药物筛选的诱导多能干细胞衍生细胞模型

Induced Pluripotent Stem Cells Derived Cellular Models for Investigating Parkinson's Disease Pathogenesis and Drug Screening.

作者信息

Liu Jihong, Zhao Wanlin, Zhang Zijuan, Ai Xilei, Cao Bing, Zhang Zhenqiang, Ma Dongrui

机构信息

The First Affiliated Hospital of Henan University of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450003, China.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China.

出版信息

Stem Cell Rev Rep. 2025 Oct;21(7):1883-1900. doi: 10.1007/s12015-025-10931-7. Epub 2025 Jun 30.

DOI:10.1007/s12015-025-10931-7
PMID:40587046
Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions worldwide. The complexity of PD has hindered the development of accurate disease models. Induced pluripotent stem cells (iPSCs), derived from patient-specific cells, offer a promising platform for modeling PD. This review discusses the development of PD models using iPSCs from different patient sources, focusing on 2D and 3D culture systems. We also explore the integration of iPSCs with advanced technologies like multi-omics, tissue engineering, and gene editing, and their potential to drive breakthroughs in disease modeling. Co-culture systems of iPSC-derived neurons and glial cells provide insights into cell-cell interactions in PD, while 3D brain region-specific organoids enhance understanding of interregional disease processes. Advances in multi-omics and gene editing have further propelled iPSC-based disease modeling, offering new avenues for investigating disease mechanisms and therapeutic screening.

摘要

帕金森病(PD)是第二常见的神经退行性疾病,影响着全球数百万人。PD的复杂性阻碍了精确疾病模型的开发。源自患者特异性细胞的诱导多能干细胞(iPSC)为构建PD模型提供了一个有前景的平台。本综述讨论了使用来自不同患者来源的iPSC构建PD模型的进展,重点关注二维和三维培养系统。我们还探讨了iPSC与多组学、组织工程和基因编辑等先进技术的整合,以及它们在推动疾病建模突破方面的潜力。iPSC衍生的神经元和胶质细胞的共培养系统为PD中的细胞间相互作用提供了见解,而三维脑区特异性类器官则增强了对区域间疾病过程的理解。多组学和基因编辑的进展进一步推动了基于iPSC的疾病建模,为研究疾病机制和治疗筛选提供了新途径。

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本文引用的文献

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α-Synuclein disrupts microglial autophagy through STAT1-dependent suppression of Ulk1 transcription.α-突触核蛋白通过依赖 STAT1 的 Ulk1 转录抑制破坏小胶质细胞自噬。
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