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      Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB).

      1 ,
      Lab on a chip
      Royal Society of Chemistry (RSC)

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          Abstract

          The blood-brain barrier (BBB), a unique selective barrier for the central nervous system (CNS), hinders the passage of most compounds to the CNS, complicating drug development. Innovative in vitro models of the BBB can provide useful insights into its role in CNS disease progression and drug delivery. Static transwell models lack fluidic shear stress, while the conventional dynamic in vitro BBB lacks a thin dual cell layer interface. To address both limitations, we developed a microfluidic blood-brain barrier (μBBB) which closely mimics the in vivo BBB with a dynamic environment and a comparatively thin culture membrane (10 μm). To test validity of the fabricated BBB model, μBBBs were cultured with b.End3 endothelial cells, both with and without co-cultured C8-D1A astrocytes, and their key properties were tested with optical imaging, trans-endothelial electrical resistance (TEER), and permeability assays. The resultant imaging of ZO-1 revealed clearly expressed tight junctions in b.End3 cells, Live/Dead assays indicated high cell viability, and astrocytic morphology of C8-D1A cells were confirmed by ESEM and GFAP immunostains. By day 3 of endothelial culture, TEER levels typically exceeded 250 Ω cm(2) in μBBB co-cultures, and 25 Ω cm(2) for transwell co-cultures. Instantaneous transient drop in TEER in response to histamine exposure was observed in real-time, followed by recovery, implying stability of the fabricated μBBB model. Resultant permeability coefficients were comparable to previous BBB models, and were significantly increased at higher pH (>10). These results demonstrate that the developed μBBB system is a valid model for some studies of BBB function and drug delivery.

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          Author and article information

          Journal
          Lab Chip
          Lab on a chip
          Royal Society of Chemistry (RSC)
          1473-0189
          1473-0189
          Apr 24 2012
          : 12
          : 10
          Affiliations
          [1 ] Department of Bioengineering, University of Utah, MEB-1445, 50 S Central Campus Dr, Salt Lake City, UT 84112, USA. Ross.Booth@utah.edu
          Article
          10.1039/c2lc40094d
          22422217
          58adaf57-6290-40cc-ab1f-19dc3c55783c
          History

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