A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. iPSCs Differentiation to iBMECs
2.3. BBB on a Chip
2.4. Permeability Measurement of Sucrose and Mannitol
2.5. Immunofluorescence Microscopy
2.6. Dynamic Flow and Shear Stress
2.7. Efflux Study of the Chip
2.8. BBB Opening Using the Hyperosmolar Solution
2.9. Statistical Analyses
3. Results
3.1. Characterization of the Blood-Brain Barrier Microfluid Model
3.2. Assessment of Paracellular Permeability across a BBB Microfluidic Chip
3.3. Effect of Microfluidic Shear Stress on BBB Integrity and Barrier Function
3.4. BBB-on-a-Chip Responds to P-gp Inhibition
3.5. Hyperosmolar BBB Opening
4. Discussion
5. Conclusions and Future Studies
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
3D | three dimensional |
BBB | blood-brain barrier |
iBMECs | human brain microvascular endothelial cells derived from iPSCs |
BMECs | brain microvascular endothelial cells |
CNS | central nervous system |
CsA | cyclosporine A |
DAPI | 4′,6-diamidino-2-phenylindole |
ECM | extracellular matrix |
GFAP | glial fibrillary acidic protein |
GLUT-1 | glucose transporter |
iPSC | induced pluripotent stem cells |
LC-MS | liquid chromatography and mass spectrometry |
MRP | multidrug-resistance-associated protein |
NVU | neurovascular unit |
PDMS | polydimethylsiloxane |
P-gp | P-glycoprotein |
R123 | rhodamine 123 |
TEER | trans-endothelial electrical resistance |
TJs | tight junctions |
UPLC | ultra-performance liquid chromatography |
ZO-1 | zona occludens-1 |
α-SMA | alpha-smooth muscle actin |
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Noorani, B.; Bhalerao, A.; Raut, S.; Nozohouri, E.; Bickel, U.; Cucullo, L. A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies. Pharmaceutics 2021, 13, 1474. https://doi.org/10.3390/pharmaceutics13091474
Noorani B, Bhalerao A, Raut S, Nozohouri E, Bickel U, Cucullo L. A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies. Pharmaceutics. 2021; 13(9):1474. https://doi.org/10.3390/pharmaceutics13091474
Chicago/Turabian StyleNoorani, Behnam, Aditya Bhalerao, Snehal Raut, Ehsan Nozohouri, Ulrich Bickel, and Luca Cucullo. 2021. "A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies" Pharmaceutics 13, no. 9: 1474. https://doi.org/10.3390/pharmaceutics13091474