用于研究屏障损伤的 3D 体外血脑屏障模型,Advanced Science

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用于研究屏障损伤的 3D 体外血脑屏障模型
Advanced Science ( IF 14.3 ) Pub Date : 2023-02-13 , DOI: 10.1002/advs.202205752
Wei Wei ₁ , Fernando Cardes ₁ , Andreas Hierlemann ₁ , Mario M Modena ₁

Affiliation

血脑屏障 (BBB) 破坏与多种中枢神经系统疾病有关。体外 BBB 模型能够研究屏障如何对外部伤害事件（通常称为侮辱）做出反应。在这里，提出了一种基于人体细胞的 BBB 平台，该平台具有集成的透明电极，可以以高分辨率实时监测屏障的紧密度。BBB 模型包括人脑内皮细胞和原代周细胞和星形胶质细胞，在无泵、开放式微流体平台内以 3D 排列。借助该平台，这项研究表明，模拟缺血性损伤特征的氧-葡萄糖剥夺 (OGD) 可诱导细胞肌动蛋白结构的快速重塑和内皮细胞随后的形态变化。高分辨率实时成像显示在 OGD 应用过程中在内皮层形成大的肌动蛋白应力纤维束，最终导致细胞收缩和屏障破裂。同时电测量证明在应力纤维出现之前屏障电阻迅速下降，这表明屏障功能在剧烈形态变化出现之前就已经受到损害。结果表明，BBB 平台概括了体外的主要屏障功能，可用于研究应用外部刺激后 BBB 的快速重组。同时电测量证明在应力纤维出现之前屏障电阻迅速下降，这表明屏障功能在剧烈形态变化出现之前就已经受到损害。结果表明，BBB 平台概括了体外的主要屏障功能，可用于研究应用外部刺激后 BBB 的快速重组。同时电测量证明在应力纤维出现之前屏障电阻迅速下降，这表明屏障功能在剧烈形态变化出现之前就已经受到损害。结果表明，BBB 平台概括了体外的主要屏障功能，可用于研究应用外部刺激后 BBB 的快速重组。

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3D In Vitro Blood-Brain-Barrier Model for Investigating Barrier Insults

Blood-brain-barrier (BBB) disruption has been associated with a variety of central-nervous-system diseases. In vitro BBB models enable to investigate how the barrier reacts to external injury events, commonly referred to as insults. Here, a human-cell-based BBB platform with integrated, transparent electrodes to monitor barrier tightness in real time at high resolution is presented. The BBB model includes human cerebral endothelial cells and primary pericytes and astrocytes in a 3D arrangement within a pump-free, open-microfluidic platform. With this platform, this study demonstrates that oxygen-glucose deprivation (OGD), which mimics the characteristics of an ischemic insult, induces a rapid remodeling of the cellular actin structures and subsequent morphological changes in the endothelial cells. High-resolution live imaging shows the formation of large actin stress-fiber bundles in the endothelial layer during OGD application, which ultimately leads to cell shrinkage and barrier breakage. Simultaneous electrical measurements evidence a rapid decrease of the barrier electrical resistance before the appearance of stress fibers, which indicates that the barrier function is compromised already before the appearance of drastic morphological changes. The results demonstrate that the BBB platform recapitulates the main barrier functions in vitro and can be used to investigate rapid reorganization of the BBB upon application of external stimuli.

更新日期：2023-02-13

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