Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, Republic of Korea.
Department of Mechanical Engineering, Seoul National University, Seoul, Republic of Korea.
Methods Mol Biol. 2022;2492:251-263. doi: 10.1007/978-1-0716-2289-6_14.
Organ-on-a-chip enables human cell-based 3D tissue culture, which recapitulates the physiological structure and function of the tissue. In terms of the blood-brain barrier (BBB) modeling, the 3D structure of the vessel is essential for studying the cellular interactions among BBB composing cells and investigating the barrier function. Here, we describe a BBB-on-a-chip model with 3D perfusable human vasculature tri-cultured with pericytes and astrocytes. The culture method is based on mimicking angiogenic sprouting since the barrier formation is parallel with angiogenesis during the developmental process. This microfluidic-based 3D tri-culture system enables the comparative study on how surrounding BBB-related cells affect brain angiogenic sprouting. Moreover, the engineered perfusable vasculature is eligible for quantitative analysis on barrier function such as efflux transport system. We expect the BBB-on-a-chip could be used to enhance understanding BBB-related pathologies as well as the drug modulating barrier function of BBB.
器官芯片使基于人体细胞的 3D 组织培养成为可能，从而再现了组织的生理结构和功能。在血脑屏障 (BBB) 建模方面，血管的 3D 结构对于研究 BBB 组成细胞之间的细胞相互作用以及研究屏障功能至关重要。在这里，我们描述了一种具有 3D 可灌注人血管的 BBB 芯片模型，该模型与周细胞和星形胶质细胞共培养。该培养方法基于模拟血管生成发芽，因为在发育过程中，屏障形成与血管生成是平行的。这种基于微流控的 3D 三细胞培养系统能够比较研究周围与 BBB 相关的细胞如何影响脑血管生成发芽。此外，工程化的可灌注血管系统适合于对屏障功能（如外排转运系统）进行定量分析。我们期望 BBB 芯片能够用于增强对与 BBB 相关的病理学以及调节 BBB 屏障功能的药物的理解。
