Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.
Methods Mol Biol. 2022;2492:53-72. doi: 10.1007/978-1-0716-2289-6_3.
The blood-brain barrier (BBB) is a component of the neurovascular unit formed by specialized brain microvascular endothelial cells surrounded by astrocytes end-feet processes, pericytes, and a basement membrane. The BBB plays an important role in the maintenance of brain homeostasis and has seen a growing involvement in the pathophysiology of various neurological diseases. On the other hand, the presence of such a barrier remains an important challenge for drug delivery to treat such illnesses.Since the pioneering work describing the isolation and cultivation of primary brain microvascular cells about 50 years ago until now, the development of an in vitro model of the BBB that is scalable, capable to form tight monolayers, and predictive of drug permeability in vivo remained extremely challenging.The recent description of the use of induced pluripotent stem cells (iPSCs) as a modeling tool for neurological diseases raised momentum into the use of such cells to develop new in vitro models of the BBB. This chapter will provide an exhaustive description of the use of iPSCs as a source of cells for modeling the BBB in vitro, describe the advantages and limitations of such model, as well as describe their prospective use for disease modeling and drug permeability screening platforms.
血脑屏障 (BBB) 是神经血管单元的组成部分，由被星形胶质细胞终足过程、周细胞和基膜包围的特化脑微血管内皮细胞形成。BBB 在维持脑内环境稳定方面发挥着重要作用，并且在各种神经疾病的病理生理学中越来越受到关注。另一方面，由于这种屏障的存在，药物输送仍然是治疗此类疾病的重要挑战。自大约 50 年前描述原代脑微血管细胞的分离和培养的开创性工作以来，开发可扩展、能够形成紧密单层且可预测体内药物通透性的 BBB 体外模型仍然极具挑战性。最近描述了诱导多能干细胞 (iPSC) 作为神经疾病建模工具的使用，这为使用此类细胞开发新的 BBB 体外模型提供了动力。本章将全面描述使用 iPSC 作为体外 BBB 模型细胞的来源，描述该模型的优点和局限性，并描述它们在疾病建模和药物通透性筛选平台中的预期用途。
