SyM-BBB: a microfluidic blood brain barrier model

被引:256
作者
Prabhakarpandian, Balabhaskar [1 ]
Shen, Ming-Che [1 ]
Nichols, Joseph B. [1 ]
Mills, Ivy R. [1 ]
Sidoryk-Wegrzynowicz, Marta [2 ]
Aschner, Michael [2 ,3 ,4 ]
Pant, Kapil [1 ]
机构
[1] CFD Res Corp, Biomed Technol, Huntsville, AL 35805 USA
[2] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA
基金
美国国家卫生研究院;
关键词
MICROVESSEL ENDOTHELIAL-CELLS; IN-VITRO MODEL; RAT-BRAIN; FUNCTIONAL EXPRESSION; TRANSPORT; CULTURE; RBE4; PERMEABILITY; DISEASE;
D O I
10.1039/c2lc41208j
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Current techniques for mimicking the Blood-Brain Barrier (BBB) largely use incubation chambers (Transwell) separated with a filter and matrix coating to represent and to study barrier permeability. These devices have several critical shortcomings: (a) they do not reproduce critical microenvironmental parameters, primarily anatomical size or hemodynamic shear stress, (b) they often do not provide real-time visualization capability, and (c) they require a large amount of consumables. To overcome these limitations, we have developed a microfluidics based Synthetic Microvasculature model of the Blood-Brain Barrier (SyM-BBB). The SyM-BBB platform is comprised of a plastic, disposable and optically clear microfluidic chip with a microcirculation sized two-compartment chamber. The chamber is designed in such a way as to permit the realization of side-by-side apical and basolateral compartments, thereby simplifying fabrication and facilitating integration with standard instrumentation. The individually addressable apical side is seeded with endothelial cells and the basolateral side can support neuronal cells or conditioned media. In the present study, an immortalized Rat Brain Endothelial cell line (RBE4) was cultured in SyM-BBB with a perfusate of Astrocyte Conditioned Media (ACM). Biochemical analysis showed upregulation of tight junction molecules while permeation studies showed an intact BBB. Finally, transporter assay was successfully demonstrated in SyM-BBB indicating a functional model.
引用
收藏
页码:1093 / 1101
页数:9
相关论文
共 37 条
[1]   Protein expression of brain endothelial cell E-cadherin after hypoxia/aglycemia: influence of astrocyte contact [J].
Abbruscato, TJ ;
Davis, TP .
BRAIN RESEARCH, 1999, 842 (02) :277-286
[2]  
Aschner M, 2002, BRAIN PATHOL, V12, P475
[3]   BOVINE BRAIN MICROVESSEL ENDOTHELIAL-CELL MONOLAYERS AS A MODEL SYSTEM FOR THE BLOOD-BRAIN-BARRIER [J].
AUDUS, KL ;
BORCHARDT, RT .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 507 :9-18
[4]  
BARANCZYKKUZMA A, 1986, J NEUROCHEM, V46, P1956
[5]  
Begley DJ, 1996, J NEUROCHEM, V67, P988
[6]   ISOLATION AND CULTURE OF HUMAN BRAIN MICROVESSEL ENDOTHELIAL-CELLS FOR THE STUDY OF BLOOD-BRAIN-BARRIER PROPERTIES IN-VITRO [J].
BIEGEL, D ;
SPENCER, DD ;
PACHTER, JS .
BRAIN RESEARCH, 1995, 692 (1-2) :183-189
[7]  
BIEGEL D, 1994, IN VITRO CELL DEV-AN, V30A, P581
[8]   Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB) [J].
Booth, Ross ;
Kim, Hanseup .
LAB ON A CHIP, 2012, 12 (10) :1784-1792
[9]   Parameter optimization for an ICP deep silicon etching system [J].
Chen, S. C. ;
Lin, Y. C. ;
Wu, J. C. ;
Horng, L. ;
Cheng, C. H. .
MICROSYSTEM TECHNOLOGIES-MICRO-AND NANOSYSTEMS-INFORMATION STORAGE AND PROCESSING SYSTEMS, 2007, 13 (5-6) :465-474
[10]  
Cucullo L, 2005, CURR OPIN DRUG DISC, V8, P89