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Title: 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. As a result, the design of this platform is a valuable tool for studying BBB function as well as for screening of novel therapeutics.

Authors:
ORCiD logo [1];  [1];  [2];  [1];  [3];  [1];  [1];  [1]; ORCiD logo [1];  [1];  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); San Jose State Univ., San Jose, CA (United States)
  3. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Millipore Sigma, Hayward, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1583040
Report Number(s):
LLNL-JRNL-758697
Journal ID: ISSN 0090-6964; 946385
Grant/Contract Number:  
AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Annals of Biomedical Engineering
Additional Journal Information:
Journal Volume: 48; Journal Issue: 2; Journal ID: ISSN 0090-6964
Publisher:
Springer
Country of Publication:
United States
Language:
English
Subject:
42 ENGINEERING; Blood–brain barrier; Endothelial cells; Organ-on-a-chip

Citation Formats

Moya, Monica L., Triplett, Michael, Simon, Melinda, Alvarado, Javier, Booth, Ross, Osburn, Joanne, Soscia, David, Qian, Fang, Fischer, Nicholas O., Kulp, Kristen, and Wheeler, Elizabeth K. A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier. United States: N. p., 2019. Web. doi:10.1007/s10439-019-02405-y.
Moya, Monica L., Triplett, Michael, Simon, Melinda, Alvarado, Javier, Booth, Ross, Osburn, Joanne, Soscia, David, Qian, Fang, Fischer, Nicholas O., Kulp, Kristen, & Wheeler, Elizabeth K. A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier. United States. doi:10.1007/s10439-019-02405-y.
Moya, Monica L., Triplett, Michael, Simon, Melinda, Alvarado, Javier, Booth, Ross, Osburn, Joanne, Soscia, David, Qian, Fang, Fischer, Nicholas O., Kulp, Kristen, and Wheeler, Elizabeth K. Mon . "A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier". United States. doi:10.1007/s10439-019-02405-y.
@article{osti_1583040,
title = {A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier},
author = {Moya, Monica L. and Triplett, Michael and Simon, Melinda and Alvarado, Javier and Booth, Ross and Osburn, Joanne and Soscia, David and Qian, Fang and Fischer, Nicholas O. and Kulp, Kristen and Wheeler, Elizabeth K.},
abstractNote = {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. As a result, the design of this platform is a valuable tool for studying BBB function as well as for screening of novel therapeutics.},
doi = {10.1007/s10439-019-02405-y},
journal = {Annals of Biomedical Engineering},
number = 2,
volume = 48,
place = {United States},
year = {2019},
month = {11}
}

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