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A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier

Abstract

Much of what is currently known about the role of the blood–brain barrier (BBB) in regulating the passage of chemicals from the blood stream to the central nervous system (CNS) comes from animal in vivo models (requiring extrapolation to human relevance) and 2D static in vitro systems, which fail to capture the rich cell–cell and cell–matrix interactions of the dynamic 3D in vivo tissue microenvironment. In this work we have developed a BBB platform that allows for a high degree of customization in cellular composition, cellular orientation, and physiologically-relevant fluid dynamics. The system characterized and presented in this study reproduces key characteristics of a BBB model (e.g. tight junctions, efflux pumps) allowing for the formation of a selective and functional barrier. We demonstrate that our in vitro BBB is responsive to both biochemical and mechanical cues. This model further allows for culture of a CNS-like space around the BBB. The design of this platform is a valuable tool for studying BBB function as well as for screening of novel therapeutics.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgments

This work was funded by LDRD Awards 14-SI-001 and 17-SI-002 under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 Lawrence Livermore National Security, LLC. We acknowledge Scott Erickson, Sierra Levenson, Jonathan Adorno, and Haley Sandvik for their help with device fabrication efforts. LLNL-JRNL-758697.

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MM wrote the main manuscript text, analyzed the data and prepared all the figures. MM, RB, JA, MS, and MT assisted with design and fabrication of the devices. MM, JA and JO assisted with cell culture experiments. MT and DS designed the fluidic set-up. RB, FQ, MM provided input on initial device design. NF, KK and EW oversaw the project. All authors provided input for the manuscript.

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Correspondence to Monica L. Moya.

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Moya, M.L., Triplett, M., Simon, M. et al. A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier. Ann Biomed Eng 48, 780–793 (2020). https://doi.org/10.1007/s10439-019-02405-y

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Keywords

  • Blood–brain barrier
  • Endothelial cells
  • Organ-on-a-chip