Defined Differentiation of Human Pluripotent Stem Cells to Brain Microvascular Endothelial-Like Cells for Modeling the Blood-Brain Barrier.
Defined Differentiation of Human Pluripotent Stem Cells to Brain Microvascular Endothelial-Like Cells for Modeling the Blood-Brain Barrier.
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DOI：
10.1007/978-1-0716-3287-1_10
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发表时间：
2023
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血脑屏障（BBB）包括脑微血管内皮细胞（BMEC），其形成将血液隔室与脑实质分开的高阻力细胞界面。一个完整的血脑屏障是维持大脑稳态的关键，但也阻碍了神经治疗剂的进入。然而，人类特异性BBB渗透性测试的选择有限。人类多能干细胞模型为体外解剖这种屏障的组成部分提供了一个强大的工具，包括了解BBB功能的机制，以及开发改善靶向脑的分子和细胞治疗的渗透性的策略。在这里，我们提供了一个详细的，一步一步的方案，用于将人多能干细胞（hPSC）分化为表现出BMEC关键特征的细胞，包括能够模拟人BBB的细胞旁和跨细胞转运阻力和转运蛋白功能。
The blood-brain barrier (BBB) comprises brain microvascular endothelial cells (BMECs) that form a high resistance cellular interface that separates the blood compartment from the brain parenchyma. An intact BBB is pivotal to maintaining brain homeostasis, but also impedes the entry of neurotherapeutics. There are limited options for human-specific BBB permeability testing, however. Human pluripotent stem cell models offer a powerful tool for dissecting components of this barrier in vitro, including understanding mechanisms of BBB function, and developing strategies to improve the permeability of molecular and cellular therapeutics targeting the brain. Here, we provide a detailed, step-by-step protocol for differentiation of human pluripotent stem cells (hPSCs) to cells exhibiting key characteristics of BMECs, including paracellular and transcellular transport resistance and transporter function that enable modeling the human BBB.