Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, 1300 S. Coulter Street, Amarillo, TX, 79106, USA.
Center for Blood-Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA.
Fluids Barriers CNS. 2020 Mar 16;17(1):22. doi: 10.1186/s12987-020-00183-7.
The blood-brain barrier (BBB) is a fundamental component of the central nervous system. Its functional and structural integrity is vital in maintaining the homeostasis of the brain microenvironment. On the other hand, the BBB is also a major hindering obstacle for the delivery of effective therapies to treat disorders of the Central Nervous System (CNS). Over time, various model systems have been established to simulate the complexities of the BBB. The development of realistic in vitro BBB models that accurately mimic the physiological characteristics of the brain microcapillaries in situ is of fundamental importance not only in CNS drug discovery but also in translational research. Successful modeling of the Neurovascular Unit (NVU) would provide an invaluable tool that would aid in dissecting out the pathological factors, mechanisms of action, and corresponding targets prodromal to the onset of CNS disorders. The field of BBB in vitro modeling has seen many fundamental changes in the last few years with the introduction of novel tools and methods to improve existing models and enable new ones. The development of CNS organoids, organ-on-chip, spheroids, 3D printed microfluidics, and other innovative technologies have the potential to advance the field of BBB and NVU modeling. Therefore, in this review, summarize the advances and progress in the design and application of functional in vitro BBB platforms with a focus on rapidly advancing technologies.
血脑屏障 (BBB) 是中枢神经系统的基本组成部分。其功能和结构的完整性对于维持脑微环境的稳态至关重要。另一方面，BBB 也是将有效治疗方法递送到中枢神经系统 (CNS) 疾病部位的主要障碍。随着时间的推移，已经建立了各种模型系统来模拟 BBB 的复杂性。开发能够准确模拟原位脑微血管生理特征的真实体外 BBB 模型不仅对 CNS 药物发现具有重要意义，而且对转化研究也具有重要意义。成功模拟神经血管单元 (NVU) 将提供一个非常有价值的工具，有助于剖析 CNS 疾病发生前的病理因素、作用机制和相应靶点。在过去的几年中，随着新工具和方法的引入，以改进现有模型并开发新模型，体外 BBB 建模领域发生了许多根本性变化。CNS 类器官、芯片上器官、球体、3D 打印微流控等创新技术具有推进 BBB 和 NVU 建模领域的潜力。因此，在这篇综述中，我们总结了功能性体外 BBB 平台的设计和应用方面的进展和进步，重点介绍了快速发展的技术。
