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Microengineered human blood-brain barrier platform for understanding nanoparticle transport mechanisms.
- Source :
-
Nature communications [Nat Commun] 2020 Jan 10; Vol. 11 (1), pp. 175. Date of Electronic Publication: 2020 Jan 10. - Publication Year :
- 2020
-
Abstract
- Challenges in drug development of neurological diseases remain mainly ascribed to the blood-brain barrier (BBB). Despite the valuable contribution of animal models to drug discovery, it remains difficult to conduct mechanistic studies on the barrier function and interactions with drugs at molecular and cellular levels. Here we present a microphysiological platform that recapitulates the key structure and function of the human BBB and enables 3D mapping of nanoparticle distributions in the vascular and perivascular regions. We demonstrate on-chip mimicry of the BBB structure and function by cellular interactions, key gene expressions, low permeability, and 3D astrocytic network with reduced reactive gliosis and polarized aquaporin-4 (AQP4) distribution. Moreover, our model precisely captures 3D nanoparticle distributions at cellular levels and demonstrates the distinct cellular uptakes and BBB penetrations through receptor-mediated transcytosis. Our BBB platform may present a complementary in vitro model to animal models for prescreening drug candidates for the treatment of neurological diseases.
- Subjects :
- Animals
Aquaporin 4 metabolism
Astrocytes metabolism
Biomedical Engineering instrumentation
Cell Culture Techniques methods
Drug Delivery Systems
Drug Discovery
Flow Cytometry
Gene Expression
Gliosis
Humans
Models, Animal
Nanotechnology instrumentation
Permeability
Transcytosis
Biological Transport physiology
Biomedical Engineering methods
Blood-Brain Barrier metabolism
Lab-On-A-Chip Devices
Nanoparticles chemistry
Nanotechnology methods
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31924752
- Full Text :
- https://doi.org/10.1038/s41467-019-13896-7