Moretti Eduardo H, Lin Ally L Y, Peruzzotti-Jametti Luca, Pluchino Stefano, Mozafari Sabah
Department of Clinical Neurosciences, National Institute for Health Research (NIHR) Biomedical Research Centre, University of Cambridge, Cambridge, UK.
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
J Neurochem. 2025 Aug;169(8):e70170. doi: 10.1111/jnc.70170.
The limited regenerative capacity of the central nervous system (CNS) severely hinders treatment of neurodegenerative and neuroinflammatory diseases. These conditions, frequently exacerbated by aging, share common hallmarks such as neuroinflammation, demyelination, and neuronal loss. While neural stem cells (NSCs) hold great therapeutic promise due to their paracrine effects, including extracellular vesicle (EV) release, direct transplantation presents significant challenges. This review focuses on NSC-derived EVs as a novel therapeutic strategy, as we explore their multimodal mechanisms in modulating neuroinflammation, promoting neurogenesis, and restoring cellular bioenergetics through the delivery of bioactive molecules and mitochondrial transfer. Recent advances in NSC-EV-based therapies for age-associated neurodegenerative diseases are highlighted, along with key challenges in EV production, preservation, and targeted delivery. Finally, we outline future directions for translating this promising approach into effective clinical treatments.
中枢神经系统（CNS）有限的再生能力严重阻碍了神经退行性疾病和神经炎症性疾病的治疗。这些疾病常常因衰老而加剧，具有神经炎症、脱髓鞘和神经元丢失等共同特征。虽然神经干细胞（NSCs）因其旁分泌作用（包括释放细胞外囊泡（EVs））而具有巨大的治疗潜力，但直接移植存在重大挑战。本综述重点关注神经干细胞衍生的细胞外囊泡作为一种新型治疗策略，因为我们探讨了它们通过传递生物活性分子和线粒体转移来调节神经炎症、促进神经发生和恢复细胞生物能量学的多模式机制。文中强调了基于神经干细胞衍生细胞外囊泡治疗与年龄相关神经退行性疾病的最新进展，以及细胞外囊泡生产、保存和靶向递送方面的关键挑战。最后，我们概述了将这种有前景的方法转化为有效临床治疗的未来方向。
