Related Experiment Video
Updated: Dec 25, 2025
10:17
An In Vitro Model of the Blood-brain Barrier Using Impedance Spectroscopy: A Focus on T Cell-endothelial Cell Interaction
Published on: December 8, 2016
11.7K
Human brain microvascular endothelial cell pairs model tissue-level blood-brain barrier function.
Blakely B O'Connor1, Thomas Grevesse1, John F Zimmerman1
1Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Summary
Researchers developed a new in vitro model to predict blood-brain barrier permeability. This model uses microvascular tissue structure to assess how drugs and toxicants affect brain barrier integrity.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Cell Biology
Background:
- The blood-brain barrier (BBB) is crucial for brain health, regulating nutrient and oxygen transport while blocking toxins.
- Current in vitro models have limitations in spatial resolution and geometry, hindering accurate BBB permeability predictions.
- Predicting how substances affect BBB function is vital for drug development and toxicology.
Purpose of the Study:
- To develop and validate a novel in vitro platform for predicting blood-brain barrier (BBB) permeability.
- To correlate structural changes in human brain endothelial cells with BBB permeability states.
- To investigate the impact of pharmacological agents and nanomaterials on BBB integrity.
Main Methods:
- Utilized soft lithography to engineer microvascular tissues with controlled shapes.
- Quantified morphological changes in nuclear, junctional, and cytoskeletal proteins in endothelial cells.
- Treated cell pairs and tissues with cytoskeleton-modulating agents and measured traction forces.
- Exposed cell models to engineered nanoparticles to assess BBB disruption mechanisms.
Main Results:
- Established a correlation between endothelial cell pair structure and BBB permeability.
- Identified specific morphological indicators of high permeability, including nuclear elongation and junction protein loss.
- Demonstrated that increased intercellular junctional stress contributes to BBB leakiness.
- Uncovered mechanisms of nanoparticle-mediated BBB disruption.
Conclusions:
- The developed platform accurately predicts BBB permeability states based on endothelial cell morphology.
- This model provides insights into the multiscale effects of agents on BBB integrity.
- The platform is valuable for assessing the impact of pharmacological agents and environmental toxicants on the BBB.
