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Models of the blood-brain barrier using iPSC-derived cells.
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2020-07-24 , DOI: 10.1016/j.mcn.2020.103533
Louise Delsing 1 , Anna Herland 2 , Anna Falk 3 , Ryan Hicks 4 , Jane Synnergren 5 , Henrik Zetterberg 6
Affiliation  

The blood-brain barrier (BBB) constitutes the interface between the blood and the brain tissue. Its primary function is to maintain the tightly controlled microenvironment of the brain. Models of the BBB are useful for studying the development and maintenance of the BBB as well as diseases affecting it. Furthermore, BBB models are important tools in drug development and support the evaluation of the brain-penetrating properties of novel drug molecules. Currently used in vitro models of the BBB include immortalized brain endothelial cell lines and primary brain endothelial cells of human and animal origin. Unfortunately, many cell lines and primary cells do not recreate physiological restriction of transport in vitro. Human-induced pluripotent stem cell (iPSC)-derived brain endothelial cells have proven a promising alternative source of brain endothelial-like cells that replicate tight cell layers with low paracellular permeability. Given the possibility to generate large amounts of human iPSC-derived brain endothelial cells they are a feasible alternative when modelling the BBB in vitro. iPSC-derived brain endothelial cells form tight cell layers in vitro and their barrier properties can be enhanced through coculture with other cell types of the BBB. Currently, many different models of the BBB using iPSC-derived cells are under evaluation to study BBB formation, maintenance, disruption, drug transport and diseases affecting the BBB. This review summarizes important functions of the BBB and current efforts to create iPSC-derived BBB models in both static and dynamic conditions. In addition, it highlights key model requirements and remaining challenges for human iPSC-derived BBB models in vitro.



中文翻译:

使用 iPSC 衍生细胞的血脑屏障模型。

血脑屏障(BBB)构成了血液和脑组织之间的界面。它的主要功能是维持大脑严格控制的微环境。BBB 模型可用于研究 BBB 的发育和维持以及影响它的疾病。此外,BBB 模型是药物开发中的重要工具,支持评估新药物分子的大脑穿透特性。目前使用的 BBB体外模型包括永生化脑内皮细胞系和人和动物来源的原代脑内皮细胞。不幸的是,许多细胞系和原代细胞不能在体外重新产生运输的生理限制. 人类诱导多能干细胞 (iPSC) 衍生的脑内皮细胞已被证明是一种有前景的脑内皮样细胞替代来源,可复制具有低细胞旁通透性的紧密细胞层。鉴于产生大量人类 iPSC 衍生的脑内皮细胞的可能性,它们是体外BBB 建模的可行替代方案。iPSC 衍生的脑内皮细胞在体外形成紧密的细胞层并且它们的屏障特性可以通过与 BBB 的其他细胞类型共培养来增强。目前,正在评估使用 iPSC 衍生细胞的 BBB 的许多不同模型,以研究 BBB 的形成、维持、破坏、药物运输和影响 BBB 的疾病。本综述总结了 BBB 的重要功能以及当前在静态和动态条件下创建 iPSC 衍生 BBB 模型的努力。此外,它还强调了体外人类 iPSC 衍生 BBB 模型的关键模型要求和剩余挑战。

更新日期:2020-08-04
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