Current Status of In vitro Models of the Blood-brain Barrier.
Current Status of In vitro Models of the Blood-brain Barrier.
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DOI：
10.2174/1567201819666220303102614
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发表时间：
2022
影响因子：
2.4
通讯作者：
Dong, Xiaowei
中科院分区：
文献类型：
--
作者：
Shah, Brijesh;Dong, Xiaowei
大脑疾病是全球受影响最严重的情况，死亡率每年都在上升，而大脑生理学和繁琐的药物开发过程加剧了这一点。虽然血脑屏障(BBB)及其成分对脑保护很重要，但其复杂性给脑部药物输送造成了主要障碍，BBB是治疗失败导致疾病进展的主要原因。因此，开发一种理想的平台，能够在早期开发阶段预测药物输送系统在大脑中的行为，是极其关键的。在这方面，在过去的二十年里，研究人员开发了大量的体外血脑屏障模型，以了解屏障特性以及体外模型与体内血脑屏障的模拟程度。在体外，BBB模型主要是在二维或三维平台上培养内皮细胞或与其他血管周围细胞共培养。在这篇文章中，我们简要总结了血脑屏障的基本原理，并概述了不同类型的体外血脑屏障模型及其优缺点。根据现有的报告，似乎没有一个模型是健壮的，可以真正模拟体内BBB微血管系统的全部特性。然而，人类干细胞、共培养和三维模型被发现不完全但比其他体外模型更精确地模拟了屏障完整性的复杂性。需要更多旨在将它们结合起来的研究，以开发出一种理想的体外模型，以克服现有的局限性，并解开神秘的血脑屏障。
Disorders of the brain are the most debilitating situation affected globally with increased mortality rates every year, while brain physiology and cumbersome drug development processes exacerbate this. Although the blood-brain barrier (BBB) and its components are important for brain protection, their complexity creates major obstacles for brain drug delivery and the BBB is the primary cause of treatment failure leading to disease progression. Therefore, developing an ideal platform that can predict the behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated by researchers to understand the barrier properties and how closely the in vitro models mimic in vivo BBB. In vitro BBB models are mainly the culture of endothelial cells or their co-culture with other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the entire properties of the in vivo BBB microvasculature. However, human stem cells, co-culture, and three-dimensional models were found to mimic the complexity of the barrier integrity not completely but more precisely than other in vitro models. More studies aiming towards combining them would be needed to develop an ideal in vitro model that can overcome the existing limitations and unravel the mysterious BBB.
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