中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (11): 2132-2140.doi: 10.4103/1673-5374.310671

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

建立三维体外模型以研究神经血管单位在健康和疾病中的功

  

  • 出版日期:2021-11-15 发布日期:2021-04-13

Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

Tara M. Caffrey, Emily B. Button, Jerome Robert   

  1. 1Djavad Mowafaghian Center for Brain Health, University of British Columbia, Vancouver, BC, Canada; 2Department of Pathology, University of British Columbia, Vancouver, BC, Canada; 3Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland 
  • Online:2021-11-15 Published:2021-04-13
  • Contact: Jerome Robert, PhD, jerome.robert@usz.ch.
  • Supported by:
    This work was supported by the Weston Brain Institute Rapid Response Grant, No. RR182093 (to JR).

摘要:

Neural Regen Res:三维体外模型系统如何能够识别疾病机制和治疗靶点?

大脑的高代谢需求需要一个高效的血管系统与神经活动相结合,以提供足够的营养和氧气。这种供应是由神经元、胶质细胞和血管细胞(统称为神经血管单位)的活动协调的,这些细胞通过一种称为神经血管耦合的过程在时间和空间上调节局部脑血流。在许多神经退行性疾病中,神经血管单位功能的改变不仅损害了神经血管的耦合,而且损害了血脑屏障的通透性、脑血流量和脑废物的清除。为了研究疾病的机制,需要改进与生理相关的神经血管单位的人体模型。利用干细胞衍生的类器官和最近的血管化类器官在体外模拟神经血管单位的细胞复杂性方面取得了进展,使非细胞自主过程的复杂研究成为可能。大脑类器官形成的随机性可以在批次和方案之间产生可变的细胞组成。脑类器官的这种细胞异质性可以通过改变培养基成分来限制,从而引导细胞走向特定的命运。

来自加拿大英属哥伦比亚大学的Jerome Robert认为微流控设备和组织工程的创新设计正在提高我们对神经血管单位生物学和病理生理学的理解。不断创新建立更多生理相关的神经血管单位模型,包括细胞复杂性和设计的功能,以更清晰的展示出神经血管单位的功能。神经血管单位生理相关模型的研究进展,来自先进细胞培养系统的创新和新颖的工程设计将推动我们对神经血管单位生物学和病理生理学的理解。随着保真度的提高,模型系统能够更好地识别疾病机制和治疗靶点,并告知哪些疗法在体内有效。

文章在《中国神经再生研究(英文版)》杂志2021年 月 11 期发表。

https://orcid.org/0000-0002-2847-9362 (Jerome Robert) 

Abstract: The high metabolic demands of the brain require an efficient vascular system to be coupled with neural activity to supply adequate nutrients and oxygen. This supply is coordinated by the action of neurons, glial and vascular cells, known collectively as the neurovascular unit, which temporally and spatially regulate local cerebral blood flow through a process known as neurovascular coupling. In many neurodegenerative diseases, changes in functions of the neurovascular unit not only impair neurovascular coupling but also permeability of the blood-brain barrier, cerebral blood flow and clearance of waste from the brain. In order to study disease mechanisms, we need improved physiologically-relevant human models of the neurovascular unit. Advances towards modeling the cellular complexity of the neurovascular unit in vitro have been made using stem-cell derived organoids and more recently, vascularized organoids, enabling intricate studies of non-cell autonomous processes. Engineering and design innovations in microfluidic devices and tissue engineering are progressing our ability to interrogate the cerebrovasculature. These advanced models are being used to gain a better understanding of neurodegenerative disease processes and potential therapeutics. Continued innovation is required to build more physiologically-relevant models of the neurovascular unit encompassing both the cellular complexity and designed features to interrogate neurovascular unit functionality. 

Key words: Alzheimer’s disease, cerebrovasculature, in vitro model, neurodegeneration, neurovascular unit