Sagol School of Neuroscience , Tel Aviv University , Tel Aviv 6997801 , Israel.
Sacklar School of Medicine, Department of Human Genetics and Biochemistry , Tel Aviv University , Tel Aviv 6997801 , Israel.
Nano Lett. 2019 Jun 12;19(6):3422-3431. doi: 10.1021/acs.nanolett.8b04148. Epub 2019 Feb 27.
Exosomes, nanovesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Alhough they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents. Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson's disease, and Alzheimer's disease. We found that MSC-exo specifically targeted and accumulated in pathologically relevant murine models brains regions up to 96 h post administration, while in healthy controls they showed a diffuse migration pattern and clearance by 24 h. The neuro-inflammatory signal in pathological brains was highly correlated with MSC-exo accumulation, suggesting that the homing mechanism is inflammatory-driven. In addition, MSC-exo were selectively uptaken by neuronal cells, but not glial cells, in the pathological regions. Taken together, these findings can significantly promote the application of exosomes for therapy and targeted drug delivery in various brain pathologies.
外泌体是由不同类型细胞分泌的纳米囊泡,能够在局部或远处实现细胞间通讯。虽然已经发现外泌体可以穿过血脑屏障,但它们在大脑内的迁移和归巢能力仍未得到研究。我们最近开发了一种基于经典 X 射线计算机断层扫描(CT)优越可视化能力的方法,结合金纳米颗粒作为标记物,对体内外泌体进行纵向和定量神经影像学研究。在这里,我们使用该技术在不同的脑病理中(包括中风、自闭症、帕金森病和阿尔茨海默病)追踪了源自骨髓间充质干细胞(MSC-exo)的经鼻给予的外泌体的迁移和归巢模式。我们发现,MSC-exo 在给药后 96 小时内特异性地靶向并聚集在与病理相关的小鼠模型大脑区域,而在健康对照中,它们在 24 小时内表现出弥散性迁移模式和清除。病理脑中的神经炎症信号与 MSC-exo 的积累高度相关,表明归巢机制是炎症驱动的。此外,MSC-exo 优先被病理区域的神经元细胞摄取,而不是神经胶质细胞。综上所述,这些发现可以显著促进外泌体在各种脑病理中的治疗和靶向药物传递应用。