How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases.
How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases.
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器官芯片技术如何协助研究类淋巴系统在神经退行性疾病中的作用。
DOI：
10.3390/ijms24032171
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发表时间：
2023-01-21
影响因子：
5.6
通讯作者：
Kamm, Roger D.
中科院分区：
文献类型：
--
作者：
Spitz, Sarah;Ko, Eunkyung;Ertl, Peter;Kamm, Roger D.
由于缺乏贯穿整个人类大脑的传统淋巴系统，这鼓励了对大脑内替代清除途径的识别和研究。2012年，淋巴系统的概念出现了，淋巴系统是一个血管周围网络，通过间质将脑脊液与脑膜内的淋巴管流体连接起来。虽然其确切的作用方式尚未完全确定，但已经确定了支配溶质运输和废物清除的关键基本过程。本文简要介绍了血管周围胶质细胞依赖性清除系统，并阐明了其在神经退行性疾病中的基本作用。目前对淋巴系统的了解几乎完全是基于动物的测量，但这些测量面临着体内实验固有的某些局限性。讨论了器官芯片技术的最新进展，以展示该技术提供替代的基于人类的体外研究模型的能力。本文的重点是当前基于微流体的神经血管系统和神经退行性疾病的体外模型如何被用于(i)更深入地了解淋巴系统的作用和功能，以及（ii）确定药物干预的新机会。
The lack of a conventional lymphatic system that permeates throughout the entire human brain has encouraged the identification and study of alternative clearance routes within the cerebrum. In 2012, the concept of the glymphatic system, a perivascular network that fluidically connects the cerebrospinal fluid to the lymphatic vessels within the meninges via the interstitium, emerged. Although its exact mode of action has not yet been fully characterized, the key underlying processes that govern solute transport and waste clearance have been identified. This review briefly describes the perivascular glial-dependent clearance system and elucidates its fundamental role in neurodegenerative diseases. The current knowledge of the glymphatic system is based almost exclusively on animal-based measurements, but these face certain limitations inherent to in vivo experiments. Recent advances in organ-on-a-chip technology are discussed to demonstrate the technology’s ability to provide alternative human-based in vitro research models. Herein, the specific focus is on how current microfluidic-based in vitro models of the neurovascular system and neurodegenerative diseases might be employed to (i) gain a deeper understanding of the role and function of the glymphatic system and (ii) to identify new opportunities for pharmacological intervention.
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