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Updated: Aug 23, 2025
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A Human Blood-Brain Interface Model to Study Barrier Crossings by Pathogens or Medicines and Their Interactions with the Brain
Published on: April 9, 2019
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Developing a transwell millifluidic device for studying blood-brain barrier endothelium
Ian C Harding1, Nicholas R O'Hare2, Mark Vigliotti2
1Department of Bioengineering, Northeastern University, Boston, MA, USA.
Lab on a Chip
|November 3, 2022
Summary
This study developed a millifluidic device to model the blood-brain barrier (BBB). The device revealed that supportive cells like pericytes and astrocytes enhance BBB integrity more than flow conditions alone.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Cell Biology
Background:
- Blood-brain barrier (BBB) endothelial cell (EC) function is influenced by flow and supportive cells (pericytes, astrocytes).
- Existing BBB models often lack physiological relevance due to sub-physiological shear stress and omission of supportive cells.
Purpose of the Study:
- To develop a millifluidic device for physiologically relevant BBB research.
- To investigate the impact of pericytes and astrocytes on human brain microvascular EC (HBMEC) barrier integrity under static and flow conditions.
Main Methods:
- Developed a millifluidic device compatible with transwell inserts for reproducible shear stress exposure.
- Assessed HBMEC barrier integrity using fluorescent dextran permeability assays and claudin-5 expression.
- Co-cultured HBMEC with primary human pericytes and astrocytes under no-flow and flow (12 dynes/cm²) conditions.
Main Results:
- Astrocytes and pericytes significantly increased HBMEC barrier integrity, indicated by reduced dextran permeability and increased claudin-5 expression.
- Pericytes appeared to provide greater barrier support than astrocytes for 3 kDa dextran permeability.
- Flow conditions reduced permeability in HBMEC monolayers but not in tri-cultures, suggesting supportive cells have a greater impact.
- Flow reduced claudin-5 and occludin expression in both monolayer and tri-culture models.
- ZO-1 expression and localization increased in tri-cultures under flow, and HBMEC alignment was observed only in tri-cultures with flow.
Conclusions:
- Physiologically relevant, multicellular BBB models are essential for accurate investigation of BBB function.
- Supportive cells play a critical role in maintaining BBB integrity, potentially more so than shear stress alone.
- Both shear stress and supportive cells are necessary to observe brain EC alignment in vitro, highlighting the complexity of the neurovascular unit.
