Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS ACS Synthetic Biology Pub Date : 2024-09-20 DOI:10.1038/s41551-024-01250-2

James G Shamul,Zhiyuan Wang,Hyeyeon Gong,Wenquan Ou,Alisa M White,Diogo P Moniz-Garcia,Shuo Gu,Alisa Morss Clyne,Alfredo Quiñones-Hinojosa,Xiaoming He

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Abstract

In vitro models of the human blood-brain barrier (BBB) are increasingly used to develop therapeutics that can cross the BBB for treating diseases of the central nervous system. Here we report a meta-analysis of the make-up and properties of transwell and microfluidic models of the healthy BBB and of BBBs in glioblastoma, Alzheimer's disease, Parkinson's disease and inflammatory diseases. We found that the type of model, the culture method (static or dynamic), the cell types and cell ratios, and the biomaterials employed as extracellular matrix are all crucial to recapitulate the low permeability and high expression of tight-junction proteins of the BBB, and to obtain high trans-endothelial electrical resistance. Specifically, for models of the healthy BBB, the inclusion of endothelial cells and pericytes as well as physiological shear stresses (~10-20 dyne cm-2) are necessary, and when astrocytes are added, astrocytes or pericytes should outnumber endothelial cells. We expect this meta-analysis to facilitate the design of increasingly physiological models of the BBB.

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健康和患病血脑屏障体外模型的组成和特性的元分析。

人体血脑屏障（BBB）的体外模型越来越多地被用于开发能穿过BBB治疗中枢神经系统疾病的疗法。在此，我们报告了对健康血脑屏障以及胶质母细胞瘤、阿尔茨海默病、帕金森病和炎症性疾病中的血脑屏障的transwell和微流控模型的组成和特性进行的荟萃分析。我们发现，模型的类型、培养方法（静态或动态）、细胞类型和细胞比例以及用作细胞外基质的生物材料对再现 BBB 的低通透性和高表达紧密连接蛋白以及获得高跨内皮电阻都至关重要。具体来说，对于健康的 BBB 模型，内皮细胞和周细胞的加入以及生理剪切应力（约 10-20 达因厘米-2）是必要的，当加入星形胶质细胞时，星形胶质细胞或周细胞的数量应多于内皮细胞。我们希望这项荟萃分析能促进设计越来越多的 BBB 生理模型。

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来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.