Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device.
Modelling a Human Blood-Brain Barrier Co-Culture Using an Ultrathin Silicon Nitride Membrane-Based Microfluidic Device.
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DOI：
10.3390/ijms24065624
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发表时间：
2023-03-15
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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了解脑毛细血管内皮中受体和受体配体的囊泡运输对于开发下一代靶向神经退行性疾病的生物制剂至关重要。这些复杂的生物学问题通常通过体外模型结合各种技术来解决。在这里，我们提出了基于干细胞的人体外血脑屏障模型的开发，该模型由模块化µSiM（一种具有氮化硅膜的微型设备）平台上的诱导脑微血管内皮细胞（iBMEC）组成。µSiM配备了100 nm厚的纳米多孔氮化硅膜，具有玻璃般的成像质量，允许使用高分辨率原位成像来研究细胞内运输。作为概念验证实验，我们使用µSiM-iBMEC-人星形胶质细胞模型研究了两种单克隆抗体（mAb）的运输：抗人转铁蛋白受体mAb（15 G11）和抗basigin mAb（#52）。我们的研究结果表明，有效的内皮摄取选定的抗体，但是，没有显着的转胞吞作用时，屏障是紧密的。相反，当iBMEC没有在µSiM上形成融合屏障时，抗体在iBMEC和星形胶质细胞内积聚，表明细胞具有活跃的内吞和亚细胞分选机制，µSiM本身不会阻碍抗体转运。总之，我们的µSiM-iBMEC-人星形胶质细胞模型提供了一个具有内皮样细胞的紧密屏障，可用于高分辨率原位成像和研究生理屏障中受体介导的转运和转胞吞作用。
Understanding the vesicular trafficking of receptors and receptor ligands in the brain capillary endothelium is essential for the development of the next generations of biologics targeting neurodegenerative diseases. Such complex biological questions are often approached by in vitro models in combination with various techniques. Here, we present the development of a stem cell-based human in vitro blood-brain barrier model composed of induced brain microvascular endothelial cells (iBMECs) on the modular µSiM (a microdevice featuring a silicon nitride membrane) platform. The µSiM was equipped with a 100 nm thick nanoporous silicon nitride membrane with glass-like imaging quality that allowed the use of high-resolution in situ imaging to study the intracellular trafficking. As a proof-of-concept experiment, we investigated the trafficking of two monoclonal antibodies (mAb): an anti-human transferrin receptor mAb (15G11) and an anti-basigin mAb (#52) using the µSiM-iBMEC-human astrocyte model. Our results demonstrated effective endothelial uptake of the selected antibodies; however, no significant transcytosis was observed when the barrier was tight. In contrast, when the iBMECs did not form a confluent barrier on the µSiM, the antibodies accumulated inside both the iBMECs and astrocytes, demonstrating that the cells have an active endocytic and subcellular sorting machinery and that the µSiM itself does not hinder antibody transport. In conclusion, our µSiM-iBMEC-human astrocyte model provides a tight barrier with endothelial-like cells, which can be used for high-resolution in situ imaging and for studying receptor-mediated transport and transcytosis in a physiological barrier.
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DOI：
10.1084/jem.20211057
发表时间：
2022-03-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arguello A;Mahon CS;Calvert MEK;Chan D;Dugas JC;Pizzo ME;Thomsen ER;Chau R;Damo LA;Duque J;Fang M;Giese T;Kim DJ;Liang N;Nguyen HN;Solanoy H;Tsogtbaatar B;Ullman JC;Wang J;Dennis MS;Diaz D;Gunasekaran K;Henne KR;Lewcock JW;Sanchez PE;Troyer MD;Harris JM;Scearce-Levie K;Shan L;Watts RJ;Thorne RG;Henry AG;Kariolis MS
通讯作者：
Kariolis MS
DOI：
10.1084/jem.20131660
发表时间：
2014-02-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bien-Ly N;Yu YJ;Bumbaca D;Elstrott J;Boswell CA;Zhang Y;Luk W;Lu Y;Dennis MS;Weimer RM;Chung I;Watts RJ
通讯作者：
Watts RJ
影响因子：
10
作者：
McCloskey, Molly C.;Kasap, Pelin;Ahmad, S. Danial;Su, Shiuan-Haur;Chen, Kaihua;Mansouri, Mehran;Ramesh, Natalie;Nishihara, Hideaki;Belyaev, Yury;Abhyankar, Vinay V.;Begolo, Stefano;Singer, Benjamin H.;Webb, Kevin F.;Kurabayashi, Katsuo;Flax, Jonathan;Waugh, Richard E.;Engelhardt, Britta;McGrath, James L.
通讯作者：
McGrath, James L.
DOI：
10.1073/pnas.2016950118
发表时间：
2021-02-23
影响因子：
11.1
作者：
Lu TM;Houghton S;Magdeldin T;Durán JGB;Minotti AP;Snead A;Sproul A;Nguyen DT;Xiang J;Fine HA;Rosenwaks Z;Studer L;Rafii S;Agalliu D;Redmond D;Lis R
通讯作者：
Lis R
影响因子：
4.6
作者：
Christensen, Sarah Christine;Krogh, Berit Olsen;Nielsen, Morten Schallburg
通讯作者：
Nielsen, Morten Schallburg