A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes

被引:177
作者
Bang, Seokyoung [1 ]
Lee, Seung-Ryeol [1 ]
Ko, Jihoon [1 ]
Son, Kyungmin [1 ]
Tahk, Dongha [1 ]
Ahn, Jungho [1 ]
Im, Changkyun [2 ]
Jeon, Noo Li [1 ,3 ]
机构
[1] Seoul Natl Univ, Div WCU World Class Univ Multiscale Mech Design, Sch Mech & Aerosp Engn, Seoul, South Korea
[2] Seoul Natl Univ, Plus Transformat Training Program Creat Mech Engi, Seoul, South Korea
[3] Seoul Natl Univ, Inst Adv Machinery & Design, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
VEIN ENDOTHELIAL-CELLS; IN-VITRO MODEL; NEUROVASCULAR UNIT; VESSELS; VEGF;
D O I
10.1038/s41598-017-07416-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A novel three dimensional blood brain barrier (BBB) platform was developed by independently supplying different types of media to separate cell types within a single device. One channel (vascular channel, VC) is connected to the inner lumen of the vascular network while the other supplies media to the neural cells (neural channel, NC). Compared to co-cultures supplied with only one type of medium (or 1: 1 mixture), best barrier properties and viability were obtained with culturing HUVECs with endothelial growth medium (EGM) and neural cells with neurobasal medium supplemented with fetal bovine serum (NBMFBS) independently. The measured vascular network permeability were comparable to reported in vivo values (20 kDa FITC-dextran, 0.45 +/- 0.11 x 10(-6) cm/s; 70 kDa FITC-dextran, 0.36 +/- 0.05 x 10(-6) cm/s) and a higher degree of neurovascular interfacing (astrocytic contact with the vascular network, GFAP-CD31 stain overlap) and presence of synapses (stained with synaptophysin). The BBB platform can dependably imitate the perivascular network morphology and synaptic structures characteristic of the NVU. This microfluidic BBB model can find applications in screening pharmaceuticals that target the brain for in neurodegenerative diseases.
引用
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页数:10
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