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The blood–brain barrier (BBB) is composed of brain microvascular endothelial cells (BMECs), which form intercellular tight-junctions and express a variety of transporters and receptors to regulate the transport of substances between blood and brain. In order to develop ways to deliver drugs effectively to the brain parenchyma, it is important to understand the functional properties of the BBB. Studies in animal models are problematic, both for ethical reasons and because of species differences in the BBB function, and instead, various in vitro human BBB models have recently been constructed using BMEC-derived cell lines. Further, to reproduce the in vivo brain microenvironment more closely, microfluidic systems have been developed to impose shear stress on the component cells. This chapter focuses on the integrity of tight-junctions and the expression of functional transporters in human-derived BBB model cells and describes typical two-dimensional (2D) and three-dimensional (3D) microfluidic systems used to culture these cells. Finally, we discuss applications of our high-throughput microfluidic system with brain microvascular endothelial-like cells derived from human induced pluripotent stem cells (hiPSCs-derived BMECs).

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Construction and Functional Evaluation of 2D and 3D Human Blood–Brain Barrier Models

  • 章节

  • 发表日期：

    2025年

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  • Toshiki Kurosawa,
  • Yoshiyuki Kubo,
  • Yoshiharu Deguchi

摘要

The blood–brain barrier (BBB) is composed of brain microvascular endothelial cells (BMECs), which form intercellular tight-junctions and express a variety of transporters and receptors to regulate the transport of substances between blood and brain. In order to develop ways to deliver drugs effectively to the brain parenchyma, it is important to understand the functional properties of the BBB. Studies in animal models are problematic, both for ethical reasons and because of species differences in the BBB function, and instead, various in vitro human BBB models have recently been constructed using BMEC-derived cell lines. Further, to reproduce the in vivo brain microenvironment more closely, microfluidic systems have been developed to impose shear stress on the component cells. This chapter focuses on the integrity of tight-junctions and the expression of functional transporters in human-derived BBB model cells and describes typical two-dimensional (2D) and three-dimensional (3D) microfluidic systems used to culture these cells. Finally, we discuss applications of our high-throughput microfluidic system with brain microvascular endothelial-like cells derived from human induced pluripotent stem cells (hiPSCs-derived BMECs).