中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4529-4537.doi: 10.4103/NRR.NRR-D-25-01806

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

脑类器官是细胞外囊泡介导的人类神经通讯模型

  

  • 出版日期:2026-10-15 发布日期:2026-06-11

Brain organoids as models of extracellular vesicle–mediated human neural communication

Giuliana La Rosa1, 2, *, Erika Pascale1, Maria Roberta Iazzetta3, Edoardo Sozzi4, Annalisa Fico5, Elvira Immacolata Parrotta2, Alessandro Fiorenzano1, 6, *   

  1. 1Department of Molecular Medicine and Medical Biotechnology, University of Naples “Federico II,” Naples, Italy; 
    2Stem cell laboratory, Department of Medical and Surgical Sciences, University “Magna Graecia,” Catanzaro, Italy; 
    3Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy; 
    4Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; 
    5Stem Cell Fate Laboratory, Institute of Genetics and Biophysics ‘‘A. Buzzati-Traverso,’’ CNR, Naples, Italy; 
    6Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund Stem Cell Center, Lund University, Lund, Sweden
  • Online:2026-10-15 Published:2026-06-11
  • Contact: Giuliana La Rosa, PhD, giuliana.larosa@unicz.it or giuliana.larosa@unina.it; Alessandro Fiorenzano, PhD, alessandro.fiorenzano@med.lu.se or alessandro.fiorenzano@unina.it.
  • Supported by:
    The work was supported by The Crafoord Foundation, No. 20240532 and Swedish Research Council, No. 2022-01432 (both to AF).

摘要:

细胞通讯可通过粘附分子、信号配体、细胞外基质和细胞外囊泡的复杂相互作用来协调人脑的发育。虽然调节神经分化的内在遗传程序具有很好的特征,但对外界非细胞自主信号传导的作用,特别是细胞外介导的通信,仍然知之甚少。此次综述描述了基于人类多能干细胞构建的三维脑类器官的最新进展。该生理相关模型重现了人类神经发育的关键特征,为深入研究细胞外囊泡介导的细胞内信号传导提供了可能。文章还重点阐述类器官系统如何促进外泌体载荷动态及其对神经细胞命运、迁移和回路组装的影响研究,并揭示其在阿尔茨海默病、帕金森病等神经退行性疾病中的作用。这些发现表明脑类器官在解析复杂细胞相互作用、推动神经疾病生物标志物发现及治疗策略制定方面具有巨大潜力。


https://orcid.org/0000-0001-5704-4408 (Giuliana La Rosa); https://orcid.org/0000-0003-2478-5941 (Alessandro Fiorenzano)

关键词: 阿尔茨海默病, 淀粉样蛋白β, 脑类器官, 细胞间通讯, 细胞外囊泡, 神经变性, 神经发育, 帕金森病, 多能干细胞, α突触核蛋白

Abstract: Cellular communication orchestrates human brain development through complex interactions involving adhesion molecules, signaling ligands, extracellular matrix, and extracellular vesicles. While intrinsic genetic programs governing neural differentiation are well characterized, the roles of extrinsic, non-cell-autonomous signaling, particularly extracellular-mediated communication, remain poorly understood. Here, we review recent advances in three-dimensional brain organoids derived from human pluripotent stem cells as physiologically relevant models that recapitulate key aspects of human neurodevelopment, enabling detailed study of extracellular vesicle-mediated intracellular signaling. We highlight how organoid systems facilitate the investigation of extracellular vesicle cargo dynamics and their influence on neural cell fate, migration, and circuit assembly, as well as their involvement in neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. These insights show the potential of brain organoids to unravel complex cellular interactions and inform biomarkers discovery and therapeutic strategies for neurological diseases. 

Key words: Alzheimer’s disease, amyloid-β, brain organoid, cell–cell communication, extracellular vesicle, neurodegeneration, neurodevelopment, Parkinson’s disease, pluripotent stem cell, α-synuclein