神经血管单元的微流控模型:转化视角。

Microfluidic models of the neurovascular unit: a translational view.

机构信息

MIMETAS BV, De Limes 7, Oegstgeest, 2342 DH, The Netherlands.

Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam Neuroscience - Neuroinfection and Neuroinflammation, De Boelelaan 1117, Amsterdam, the Netherlands.

出版信息

Fluids Barriers CNS. 2023 Nov 27;20(1):86. doi: 10.1186/s12987-023-00490-9.

Abstract

The vasculature of the brain consists of specialized endothelial cells that form a blood-brain barrier (BBB). This barrier, in conjunction with supporting cell types, forms the neurovascular unit (NVU). The NVU restricts the passage of certain substances from the bloodstream while selectively permitting essential nutrients and molecules to enter the brain. This protective role is crucial for optimal brain function, but presents a significant obstacle in treating neurological conditions, necessitating chemical modifications or advanced drug delivery methods for most drugs to cross the NVU. A deeper understanding of NVU in health and disease will aid in the identification of new therapeutic targets and drug delivery strategies for improved treatment of neurological disorders.To achieve this goal, we need models that reflect the human BBB and NVU in health and disease. Although animal models of the brain's vasculature have proven valuable, they are often of limited translational relevance due to interspecies differences or inability to faithfully mimic human disease conditions. For this reason, human in vitro models are essential to improve our understanding of the brain's vasculature under healthy and diseased conditions. This review delves into the advancements in in vitro modeling of the BBB and NVU, with a particular focus on microfluidic models. After providing a historical overview of the field, we shift our focus to recent developments, offering insights into the latest achievements and their associated constraints. We briefly examine the importance of chip materials and methods to facilitate fluid flow, emphasizing their critical roles in achieving the necessary throughput for the integration of microfluidic models into routine experimentation. Subsequently, we highlight the recent strides made in enhancing the biological complexity of microfluidic NVU models and propose recommendations for elevating the biological relevance of future iterations.Importantly, the NVU is an intricate structure and it is improbable that any model will fully encompass all its aspects. Fit-for-purpose models offer a valuable compromise between physiological relevance and ease-of-use and hold the future of NVU modeling: as simple as possible, as complex as needed.

摘要

大脑的脉管系统由形成血脑屏障 (BBB) 的特化内皮细胞组成。这个屏障与支持细胞类型一起,形成了神经血管单元 (NVU)。NVU 限制了某些物质从血液中通过,同时选择性地允许必需的营养物质和分子进入大脑。这种保护作用对于最佳的大脑功能至关重要,但在治疗神经疾病方面却带来了重大障碍,需要对大多数药物进行化学修饰或采用先进的药物递送方法,才能使其穿过 NVU。深入了解 NVU 在健康和疾病中的作用,将有助于确定新的治疗靶点和药物递送策略,从而改善神经疾病的治疗效果。

为了实现这一目标,我们需要能够反映健康和疾病状态下 NVU 的模型。虽然动物脑脉管系统模型已经被证明具有价值,但由于种间差异或无法真实模拟人类疾病状态,它们往往具有有限的转化相关性。因此,人类体外模型对于提高我们对健康和疾病状态下大脑脉管系统的理解至关重要。

本综述深入探讨了 BBB 和 NVU 的体外建模进展,特别关注微流控模型。在提供该领域的历史概述后,我们将重点转移到最近的发展,深入了解最新的成就及其相关限制。我们简要探讨了芯片材料和方法在促进流体流动方面的重要性,强调了它们在实现微流控模型集成到常规实验所需的必要通量方面的关键作用。随后,我们重点介绍了在提高微流控 NVU 模型生物学复杂性方面的最新进展,并提出了一些建议,以提高未来迭代的生物学相关性。

重要的是,NVU 是一个复杂的结构,任何模型都不可能完全包含其所有方面。适合目的的模型在生理相关性和易用性之间提供了有价值的折衷,是 NVU 建模的未来方向:尽可能简单,尽可能复杂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8a/10680291/ca860fc59a83/12987_2023_490_Fig1_HTML.jpg

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