In vitro Models of the Blood–Brain Barrier: Tools in Translational Mediciney

By Alberto Williams-Medina, Michael Deblock, and Damir Janigro

Medical progress has historically depended on scientific discoveries. Until recently, science was driven by technological advancements that, once translated to the clinic, fostered new treatments and interventions. More recently, technology-driven medical progress has often outpaced laboratory research. For example, intravascular devices, pacemakers for the heart and brain, spinal cord stimulators, and surgical robots are used routinely to treat a variety of diseases. The rapid expansion of science into ever more advanced molecular and genetic mechanisms of disease has often distanced laboratory-based research from day-to-day clinical realities that remain based on evidence and outcomes. A recognized reason for this hiatus is the lack of laboratory tools that recapitulate the clinical reality faced by physicians and surgeons. To overcome this, the NIH and FDA have in the recent past joined forces to support the development of a “human-on-a-chip” that will allow research scientists to perform experiments on a realistic replica when testing the effectiveness of novel experimental therapies. The development of a “human-on-a-chip” rests on the capacity to grow in vitro various organs-on-a-chip, connected with appropriate vascular supplies and nerves, and our ability to measure and perform experiments on these virtually invisible organs. One of the tissue structures to be scaled down on a chip is the human blood–brain barrier. This review gives a historical perspective on in vitro models of the BBB and summarizes the most recent 3D models that attempt to fill the gap between research modeling and patient care. We also present a summary of how these in vitro models of the BBB can be applied to study human brain diseases and their treatments. We have chosen NeuroAIDS, COVID-19, multiple sclerosis, and Alzheimer’s disease as examples of in vitro model application to neurological disorders. Major insight pertaining to these illnesses as a consequence of more profound understanding of the BBB can reveal new avenues for the development of diagnostics, more efficient therapies, and definitive clarity of disease etiology and pathological progression.

历史上，医学进步依赖于科学发现。直到最近，科学一直受到技术进步的推动，一旦转化为临床，就会促进新的治疗和干预措施。最近，技术驱动的医学进步常常超过实验室研究。例如，血管内装置、心脏和大脑起搏器、脊髓刺激器和手术机器人通常用于治疗各种疾病。科学迅速扩展到更先进的疾病分子和遗传机制，这常常使基于实验室的研究与仍然基于证据和结果的日常临床现实相距甚远。这种中断的一个公认原因是缺乏实验室工具来概括内科医生和外科医生所面临的临床现实。为了克服这一点，NIH 和 FDA 最近联手支持开发“芯片上的人类”，这将使研究科学家在测试新型实验疗法的有效性时能够在真实的复制品上进行实验。“芯片上的人”的发展取决于在体外培养各种芯片上器官的能力，这些器官与适当的血管供应和神经相连，以及我们对这些几乎看不见的东西进行测量和实验的能力器官。在芯片上按比例缩小的组织结构之一是人体血脑屏障。这篇综述给出了 BBB 体外模型的历史观点，并总结了试图填补研究建模和患者护理之间差距的最新 3D 模型。我们还总结了如何将 BBB 的这些体外模型应用于研究人类大脑疾病及其治疗。我们选择了 NeuroAIDS、COVID-19、多发性硬化症和阿尔茨海默病作为体外模型应用于神经系统疾病的示例。由于对 BBB 的更深刻理解，与这些疾病有关的主要见解可以揭示诊断学发展的新途径、更有效的治疗以及疾病病因学和病理进展的明确清晰度。

文献原文：https://pubmed.ncbi.nlm.nih.gov/35047899/