A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes.
A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes.
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DOI：
10.1038/s41598-017-07416-0
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发表时间：
2017-08-14
影响因子：
4.6
通讯作者：
Jeon NL
中科院分区：
文献类型：
--
作者：
Bang S;Lee SR;Ko J;Son K;Tahk D;Ahn J;Im C;Jeon NL
通过在单个装置内独立供应不同类型的培养基给不同细胞类型，开发了一种新型三维血脑屏障（BBB）平台。一个通道（血管通道，VC）连接到血管网络的内腔，而另一个通道则向神经细胞供应培养基（神经通道，NC）。与仅供应一种培养基（或1:1混合培养基）的共培养相比，用内皮生长培养基（EGM）培养人脐静脉内皮细胞（HUVECs），同时用添加胎牛血清的神经基础培养基（NBMFBS）独立培养神经细胞，可获得最佳的屏障特性和细胞活力。所测量的血管网络通透性与报道的体内值相当（20 kDa异硫氰酸荧光素 - 葡聚糖，0.45 ± 0.11×10⁻⁶ cm/s；70 kDa异硫氰酸荧光素 - 葡聚糖，0.36 ± 0.05×10⁻⁶ cm/s），并且具有更高程度的神经血管连接（星形胶质细胞与血管网络接触，胶质纤维酸性蛋白 - CD31染色重叠）以及突触的存在（用突触素染色）。该血脑屏障平台能够可靠地模拟神经血管单元（NVU）特有的血管周围网络形态和突触结构。这种微流控血脑屏障模型可应用于筛选针对神经退行性疾病中大脑的药物。
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 × 10−6 cm/s; 70 kDa FITC-dextran, 0.36 ± 0.05 × 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.
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影响因子：
5.3
作者：
Mani, N;Khaibullina, A;Rosenstein, JM
通讯作者：
Rosenstein, JM
影响因子：
2.9
作者：
Cullen DK;Gilroy ME;Irons HR;Laplaca MC
通讯作者：
Laplaca MC
影响因子：
3.2
作者：
Brown, Jacquelyn A.;Pensabene, Virginia;Wikswo, John P.
通讯作者：
Wikswo, John P.
影响因子：
6.1
作者：
Kim, Sudong;Lee, Hyunjae;Jeon, Noo Li
通讯作者：
Jeon, Noo Li
影响因子：
4
作者：
Abbott, NJ
通讯作者：
Abbott, NJ