Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41467-019-12176-8 |
Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents | |
Cho, Choi-Fong1,2; Wolfe, Justin M.2; Fadzen, Colin M.2; Calligaris, David3; Hornburg, Kalvis1; Chiocca, E. Antonio1; Agar, Nathalie Y. R.3; Pentelute, Bradley L.2; Lawler, Sean E.1 | |
2019-10-02 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Culture-based blood-brain barrier (BBB) models are crucial tools to enable rapid screening of brain-penetrating drugs. However, reproducibility of in vitro barrier properties and permeability remain as major challenges. Here, we report that self-assembling multicellular BBB spheroids display reproducible BBB features and functions. The spheroid core is comprised mainly of astrocytes, while brain endothelial cells and pericytes encase the surface, acting as a barrier that regulates transport of molecules. The spheroid surface exhibits high expression of tight junction proteins, VEGF-dependent permeability, efflux pump activity and receptor-mediated transcytosis of angiopep-2. In contrast, the transwell co-culture system displays comparatively low levels of BBB regulatory proteins, and is unable to discriminate between the transport of angiopep-2 and a control peptide. Finally, we have utilized the BBB spheroids to screen and identify BBB-penetrant cell-penetrating peptides (CPPs). This robust in vitro BBB model could serve as a valuable next-generation platform for expediting the development of CNS therapeutics. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000402751800001 |
WOS关键词 | P-GLYCOPROTEIN ; MODEL ; PERMEABILITY ; HCMEC/D3 ; DELIVERY ; PROTEIN ; BBB |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204573 |
专题 | 资源环境科学 |
作者单位 | 1.Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA; 2.MIT, Dept Chem, Cambridge, MA 02139 USA; 3.Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg & Radiol, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Cho, Choi-Fong,Wolfe, Justin M.,Fadzen, Colin M.,et al. Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Cho, Choi-Fong.,Wolfe, Justin M..,Fadzen, Colin M..,Calligaris, David.,Hornburg, Kalvis.,...&Lawler, Sean E..(2019).Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents.NATURE COMMUNICATIONS,8. |
MLA | Cho, Choi-Fong,et al."Blood-brain-barrier spheroids as an in vitro screening platform for brain-penetrating agents".NATURE COMMUNICATIONS 8(2019). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论