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The field of translational cerebrovascular research routinely employs blood-brain barrier (BBB) cell models. Using in vitro culture models to accurately mimic the physiological complexity of the in vivo BBB continues to be a challenge, however. To meet this challenge, in vitro BBB models have evolved significantly over the last three decades, from static monocultures to organoids to dynamic multicellular flow-based systems. In the following chapter, we will initially focus on three key aspects that have helped to drive the evolution of in vitro BBB models, namely, (i) the availability of different cell lines and organoids that can model BBB behavior; (ii) a fuller understanding of the neurovascular unit (NVU); and (iii) an appreciation of the relevance of blood flow shear stress to BBB physiology. We will then put this knowledge into a more practical context by experimentally demonstrating two alternate means of applying physiological shear stress to primary-derived human brain microvascular endothelial cells (HBMvECs) and showing how BBB phenotype is improved in response to flow by using immunocytochemical localization of tight junction zonula occludens-1 (ZO-1) as a reporter index. The ability of applied shear to attenuate the pro-oxidant effects of inflammatory TNF-α in HBMvECs will also be demonstrated using flow cytometry, further highlighting the relevance of introducing shear into BBB models.

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In Vitro 2D and 3D Cell Models of the Human Blood-Brain Barrier: Demonstrating the Beneficial Influence of Shear Stress on Brain Microvascular Endothelial Cell Phenotype

  • 实验方案

  • 发表日期：

    2025年

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  • Keith D. Rochfort,
  • Philip M. Cummins

摘要

The field of translational cerebrovascular research routinely employs blood-brain barrier (BBB) cell models. Using in vitro culture models to accurately mimic the physiological complexity of the in vivo BBB continues to be a challenge, however. To meet this challenge, in vitro BBB models have evolved significantly over the last three decades, from static monocultures to organoids to dynamic multicellular flow-based systems. In the following chapter, we will initially focus on three key aspects that have helped to drive the evolution of in vitro BBB models, namely, (i) the availability of different cell lines and organoids that can model BBB behavior; (ii) a fuller understanding of the neurovascular unit (NVU); and (iii) an appreciation of the relevance of blood flow shear stress to BBB physiology. We will then put this knowledge into a more practical context by experimentally demonstrating two alternate means of applying physiological shear stress to primary-derived human brain microvascular endothelial cells (HBMvECs) and showing how BBB phenotype is improved in response to flow by using immunocytochemical localization of tight junction zonula occludens-1 (ZO-1) as a reporter index. The ability of applied shear to attenuate the pro-oxidant effects of inflammatory TNF-α in HBMvECs will also be demonstrated using flow cytometry, further highlighting the relevance of introducing shear into BBB models.