Modeling the Blood-Brain Barrier Using Human-Induced Pluripotent Stem Cells.

Modeling the Blood-Brain Barrier Using Human-Induced Pluripotent Stem Cells.
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使用人类诱导的多能干细胞模拟血脑屏障。

DOI:
10.1007/978-1-0716-3287-1_11
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发表时间:
2023
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
通讯作者:
Blanchard,JoelW
Blanchard,JoelW
中科院分区:
--
文献类型:
--
作者:
Mesentier-Louro,LouiseA;Suhy,Natalie;Broekaart,Diede;Bula,Michael;Pereira,AnaC;Blanchard,JoelW

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血脑屏障(BBB)是大脑的关键生理组成部分,保护大脑免受外周过程和病原体的侵害。血脑屏障是一个动态结构,与脑血流、血管生成和其他神经功能密切相关。然而,血脑屏障也为治疗药物进入大脑创造了一个具有挑战性的障碍,阻止了超过 98% 的药物与大脑的接触。神经血管合并症在包括阿尔茨海默氏症和帕金森氏病在内的多种神经系统疾病中很常见,这表明血脑屏障功能障碍或崩溃可能在神经退行性疾病中起因果作用。然而,由于人类血脑屏障组织的获取有限,人类血脑屏障在疾病中形成、维持和退化的机制仍然很大程度上未知。为了解决这些局限性,我们开发了一种源自多能干细胞的体外诱导人 BBB (iBBB)。 iBBB 模型可用于发现疾病机制、药物靶点、药物筛选和药物化学研究,以优化中枢神经系统治疗的大脑渗透。在本章中,我们将解释从诱导多能干细胞中区分三种细胞成分(内皮细胞、周细胞和星形胶质细胞)的步骤,以及如何将它们组装成 iBBB。
The blood-brain barrier (BBB) is a key physiological component of the brain, protecting the brain from peripheral processes and pathogens. The BBB is a dynamic structure that is heavily involved in cerebral blood flow, angiogenesis, and other neural functions. However, the BBB also creates a challenging barrier for the entry of therapeutics into the brain, blocking more than 98% of drugs from contact with the brain. Neurovascular comorbidities are common in several neurological diseases including Alzheimer’s and Parkinson’s Disease, suggesting that BBB dysfunction or break down likely has a causal role in neurodegeneration. However, the mechanisms by which the human BBB is formed, maintained, and degenerated in diseases remain largely unknown due to limited access to human BBB tissue. To address these limitations, we have developed an in vitro induced human BBB (iBBB) derived from pluripotent stem cells. The iBBB model can be used for discovery of disease mechanisms, drug targets, drug screening, and medicinal chemistry studies to optimize brain penetration of central nervous system therapeutics. In this chapter, we will explain the steps to differentiate the three cellular components (endothelial cells, pericytes, and astrocytes) from induced pluripotent stem cells, and how to assemble them into the iBBB.
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