Modular Tissue-in-a-CUBE Platform to Model Blood-brain-Barrier (BBB) and Brain Interaction
Modular Tissue-in-a-CUBE Platform to Model Blood-brain-Barrier (BBB) and Brain Interaction
复制标题
用于模拟血脑屏障 (BBB) 和大脑相互作用的模块化立方体组织平台
DOI：
10.1101/2023.02.25.529996
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hagiwara Masaya
中科院分区：
文献类型：
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作者：
Koh Isabel;Hagiwara Masaya
随着越来越复杂的有机化合物的出现，人们对复制多个组织或器官之间的相互作用的技术的需求越来越大。然而，由于构成每个组织的不同细胞类型的培养条件不同，实现这一目标具有挑战性。目前的方法通常需要复杂的微流控装置，但脆弱的组织样本往往不适合粗暴的处理。此外，要复制的人类系统越复杂，模型就变得越难操作。在这里，我们介绍了一种多组织芯片平台的开发，该平台利用了立方体设备的模块化和方便的处理能力。我们首次通过将星形胶质细胞、周细胞和脑微血管内皮细胞分层在立方体中开发了血脑屏障，并证实了重要的紧密连接和转运蛋白在血脑屏障模型中的表达和功能。然后，我们展示了将立方体组织与芯片相结合在模拟药物通过血脑屏障对脑的渗透性的体外测试中的应用，以及它在治疗脑胶质母细胞瘤脑癌模型中的作用。我们预计，该平台可以通过组合多个简单的立方体单元，在体外与有机化合物一起使用来构建复杂的人体系统。
With the advent of increasingly sophisticated organoids, there is growing demand for technology to replicate the interactions between multiple tissues or organs. This is challenging to achieve, however, due to the varying culture conditions of the different cell types that make up each tissue. Current methods often require complicated microfluidic setups, but fragile tissue samples tend not to fare well with rough handling. Furthermore, the more complicated the human system to be replicated, the more difficult the model becomes to operate. Here, we present the development of a multi-tissue chip platform that takes advantage of the modularity and convenient handling ability of a CUBE device. We first developed a blood-brain barrier-in-a-CUBE by layering astrocytes, pericytes, and brain microvascular endothelial cells in the CUBE, and confirmed the expression and function of important tight junction and transporter proteins in the blood-brain barrier model. Then, we demonstrated the application of integrating Tissue-in-a-CUBE with a chip in simulating the in vitro testing of the permeability of a drug through the blood-brain barrier to the brain and its effect on treating the glioblastoma brain cancer model. We anticipate that this platform can be adapted for use with organoids to build complex human systems in vitro by the combination of multiple simple CUBE units.