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基于微流控的血脑屏障(BBB)芯片在体外药物开发中的潜在应用。

Potential applications of microfluidics based blood brain barrier (BBB)-on-chips for in vitro drug development.

机构信息

Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

出版信息

Biomed Pharmacother. 2020 Dec;132:110822. doi: 10.1016/j.biopha.2020.110822. Epub 2020 Oct 12.

DOI:10.1016/j.biopha.2020.110822
PMID:33059264
Abstract

The human blood-brain barrier (BBB) is a complex multi-dimensional reticular barrier system composed of cerebral microvascular endothelial cells, pericytes, astrocytes and a variety of neurons. The conventional in vitro cell culture model fails to truly present the dynamic hemodynamics of BBB and the interaction between neurons. And it is even more impossible to explore brain-related multi-organ diseases, which brings huge obstacles to explore diseases of the central nervous system and the interaction between brain-related multi-organs, and evaluate drug efficacy. Miniaturized microfluidics based BBB chips are being commonly used to co-culture a variety of cells on a small-sized chip to construct a three-dimensional (3D) BBB or BBB-related organ disease models. By combining with other electrophysiological, biochemical sensors or equipment and imaging systems, it can in real time and quickly screen disease-related markers and evaluate drug efficacy. This review systematically summarized the research progress of in vitro BBB and BBB-related organ chips, and analyzed the obstacles of BBB models in depth. Parallelly combined with the current research trends and hot spots, we give the further improvement measures of microfluidic BBB chips.

摘要

人体血脑屏障(BBB)是一个复杂的多维网状屏障系统,由脑微血管内皮细胞、周细胞、星形胶质细胞和多种神经元组成。传统的体外细胞培养模型无法真实呈现 BBB 的动态血液动力学和神经元之间的相互作用。更不可能探索与大脑相关的多器官疾病,这给探索中枢神经系统疾病和脑相关多器官之间的相互作用以及评估药物疗效带来了巨大的障碍。基于微流控的小型化 BBB 芯片常用于在小型芯片上共培养多种细胞,构建三维(3D)BBB 或 BBB 相关器官疾病模型。通过与其他电生理、生化传感器或设备和成像系统相结合,可以实时快速筛选疾病相关标志物并评估药物疗效。本文系统总结了体外 BBB 和 BBB 相关器官芯片的研究进展,并深入分析了 BBB 模型存在的障碍。同时结合当前的研究趋势和热点,给出了微流控 BBB 芯片的进一步改进措施。

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