Organ-On-A-Chip Models of the Blood-Brain Barrier: Recent Advances and Future Prospects.
Organ-On-A-Chip Models of the Blood-Brain Barrier: Recent Advances and Future Prospects.
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DOI：
10.1002/smll.202201401
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发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
Khademhosseini A
中科院分区：
文献类型：
--
作者：
Kawakita S;Mandal K;Mou L;Mecwan MM;Zhu Y;Li S;Sharma S;Hernandez AL;Nguyen HT;Maity S;de Barros NR;Nakayama A;Bandaru P;Ahadian S;Kim HJ;Herculano RD;Holler E;Jucaud V;Dokmeci MR;Khademhosseini A
人脑和中枢神经系统（CNS）对神经系统疾病的药物开发提出了独特的挑战。其中一个主要障碍是血脑屏障（BBB），它阻碍了治疗分子有效输送到大脑中，同时保护大脑免受血源性神经毒性物质的影响并维持中枢神经系统稳态。对于 BBB 研究，传统的体外模型依赖于培养皿或 Transwell 系统。然而，这些静态模型缺乏必要的微环境因素，例如剪切应力和适当的细胞间相互作用。为此，芯片器官（OoC）技术作为一种新的体外建模方法应运而生，可以更好地重现高度动态的体内人脑微环境，即所谓的神经血管单元（NVU）。这种 BBB 芯片模型在过去十年中取得了实质性进展，同时人们对使用 OoC 技术建模各种神经系统疾病（例如阿尔茨海默病和帕金森病）的兴趣也越来越大。此外，随着其他科学技术的最新进展，我们看到了通过多学科方法改进 BBB 芯片平台的一些新机会。在这篇综述中，我们概述了 NVU 和 OoC 技术，讨论了 BBB-on-a-chip 在个性化医疗和药物发现方面的最新进展和应用，并描绘了当前的挑战和未来的方向。器官芯片技术已成为一种新的体外建模方法，可重现人类血脑屏障（BBB）。芯片上的 BBB 在过去十年中取得了实质性进展，并被用于模拟各种神经系统疾病。在这篇综述中，我们概述了 BBB 芯片模型，讨论了最新进展和关键应用，提出了当前的挑战，并提出了未来的方向。
The human brain and central nervous system (CNS) present unique challenges to drug development for neurological diseases. One major obstacle is the blood-brain barrier (BBB), which hampers the effective delivery of therapeutic molecules into the brain while protecting it from blood-born neurotoxic substances and maintaining CNS homeostasis. For BBB research, traditional in vitro models rely upon Petri dishes or Transwell systems. However, these static models lack essential microenvironmental factors such as shear stress and proper cell-cell interactions. To this end, organ-on-a-chip (OoC) technology has emerged as a new in vitro modeling approach to better recapitulate the highly dynamic in vivo human brain microenvironment so-called the neural vascular unit (NVU). Such BBB-on-a-chip models have made substantial progress over the last decade, and concurrently there has been increasing interest in modeling various neurological diseases such as Alzheimer’s disease and Parkinson’s disease using OoC technology. In addition, with recent advances in other scientific technologies, we have seen several new opportunities to improve the BBB-on-a-chip platform via multidisciplinary approaches. In this review, we provide an overview of the NVU and OoC technology, discuss recent progress and applications of BBB-on-a-chip for personalized medicine and drug discovery, and delineate current challenges and future directions. Organ-on-a-chip technology has emerged as a new in vitro modeling approach to recapitulate the human blood-brain barrier (BBB). BBB-on-a-chip has made substantial progress over the last decade and been used to model various neurological diseases. In this review, we provide an overview of the BBB-on-a-chip models, discuss recent progress and key applications, present current challenges, and propose future directions.
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影响因子：
82.9
作者：
Blanchard JW;Bula M;Davila-Velderrain J;Akay LA;Zhu L;Frank A;Victor MB;Bonner JM;Mathys H;Lin YT;Ko T;Bennett DA;Cam HP;Kellis M;Tsai LH
通讯作者：
Tsai LH
影响因子：
5.5
作者：
Bose R;Banerjee S;Dunbar GL
通讯作者：
Dunbar GL
影响因子：
14
作者：
通讯作者：
--
影响因子：
11.2
作者：
BOWMAN, PD;ENNIS, SR;GOLDSTEIN, GW
通讯作者：
GOLDSTEIN, GW
影响因子：
16.6
作者：
Bassil R;Shields K;Granger K;Zein I;Ng S;Chih B
通讯作者：
Chih B