Interstitial flow enhances the formation, connectivity, and function of 3D brain microvascular networks generated within a microfluidic device.
Interstitial flow enhances the formation, connectivity, and function of 3D brain microvascular networks generated within a microfluidic device.
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间质流增强了微流体设备中生成的3D脑微血管网络的形成，连通性和功能。
DOI：
10.1039/d1lc00605c
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发表时间：
2021-12-21
期刊：
影响因子：
6.1
通讯作者：
中科院分区：
文献类型：
--
作者：
组织间液的大量流动是人类生物学的一个重要因素，包括脑微血管网络 (MVN) 与血脑屏障 (BBB) 的发育。生物工程灌注的功能性脑 MVN 在模拟神经血管疾病和药物输送方面具有巨大潜力。然而，大多数脑 MVN 的体外模型在微血管生成过程中并未实现间质流动。使用微流体装置 (MFD)，我们在具有（流动）和不具有（静态）间质流的 3D 纤维蛋白基质内培养原代人脑内皮细胞 (BEC)、周细胞和星形胶质细胞。我们发现间质液的大量流动有利于 BEC 血管生成和血管发生。在流动条件下培养的脑 MVN 实现了吻合并可灌注，而在静态条件下培养的脑 MVN 缺乏连接性和灌注能力。与静态培养相比，流式培养中培养的微血管表现出更大的血管面积、分支长度和直径、连通性和寿命。尽管微血管的周细胞覆盖率没有变化，但在流动条件下观察到星形胶质细胞覆盖率略有增加。此外，基底层蛋白、IV 型胶原蛋白和层粘连蛋白的免疫荧光强度在流式培养中几乎加倍。最后，脑微血管的屏障功能在流动条件下得到增强，如右旋糖酐通透性降低所证明的那样。总而言之，这些结果强调了间质流在体外生成具有与人类 BBB 相似特征的灌注脑 MVN 中的重要性。
The bulk flow of interstitial fluid through tissue is an important factor in human biology, including the development of brain microvascular networks (MVNs) with the blood-brain barrier (BBB). Bioengineering perfused, functional brain MVNs has great potential for modeling neurovascular diseases and drug delivery. However, most in vitro models of brain MVNs do not implement interstitial flow during the generation of microvessels. Using a microfluidic device (MFD), we cultured primary human brain endothelial cells (BECs), pericytes, and astrocytes within a 3D fibrin matrix with (flow) and without (static) interstitial flow. We found that the bulk flow of interstitial fluid was beneficial for both BEC angiogenesis and vasculogenesis. Brain MVNs cultured under flow conditions achieved anastomosis and were perfusable, whereas those under static conditions lacked connectivity and the ability to be perfused. Compared to static culture, microvessels developed in flow culture exhibited enhanced vessel area, branch length and diameter, connectivity, and longevity. Although there was no change in pericyte coverage of microvessels, a slight increase in astrocyte coverage was observed in flow conditions. In addition, the immunofluorescence intensity of basal lamina proteins, collagen IV and laminin, was nearly doubled in flow culture. Lastly, the barrier function of brain microvessels was enhanced under flow conditions, as demonstrated by decreased dextran permeability. Taken together, these results highlighted the importance of interstitial flow in the in vitro generation of perfused brain MVNs with characteristics similar to those of the human BBB.
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影响因子：
6.1
作者：
Alonzo LF;Moya ML;Shirure VS;George SC
通讯作者：
George SC
影响因子：
4.6
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Jeon NL
影响因子：
7
作者：
Beguin, Eelke P.;Janssen, Esmee F. J.;van den Biggelaar, Maartje
通讯作者：
van den Biggelaar, Maartje
影响因子：
2.7
作者：
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通讯作者：
Messier, Claude
影响因子：
4.2
作者：
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通讯作者：
Verbeek MM