A silicon nanomembrane platform for the visualization of immune cell trafficking across the human blood-brain barrier under flow.
Blood–brain barrier
T-cell migration
microfluidics
nanoporous silicon nitride membrane
two-compartmental flow chamber
Journal
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
ISSN: 1559-7016
Titre abrégé: J Cereb Blood Flow Metab
Pays: United States
ID NLM: 8112566
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
pubmed:
20
12
2018
medline:
11
3
2020
entrez:
20
12
2018
Statut:
ppublish
Résumé
Here we report on the development of a breakthrough microfluidic human in vitro cerebrovascular barrier (CVB) model featuring stem cell-derived brain-like endothelial cells (BLECs) and nanoporous silicon nitride (NPN) membranes (µSiM-CVB). The nanoscale thinness of NPN membranes combined with their high permeability and optical transparency makes them an ideal scaffold for the assembly of an in vitro microfluidic model of the blood-brain barrier (BBB) featuring cellular elements of the neurovascular unit (NVU). Dual-chamber devices divided by NPN membranes yield tight barrier properties in BLECs and allow an abluminal pericyte-co-culture to be replaced with pericyte-conditioned media. With the benefit of physiological flow and superior imaging quality, the µSiM-CVB platform captures each phase of the multi-step T-cell migration across the BBB in live cell imaging. The small volume of <100 µL of the µSiM-CVB will enable in vitro investigations of rare patient-derived immune cells with the human BBB. The µSiM-CVB is a breakthrough in vitro human BBB model to enable live and high-quality imaging of human immune cell interactions with the BBB under physiological flow. We expect it to become a valuable new tool for the study of cerebrovascular pathologies ranging from neuroinflammation to metastatic cancer.
Identifiants
pubmed: 30565961
doi: 10.1177/0271678X18820584
pmc: PMC6421249
doi:
Substances chimiques
Membranes, Artificial
0
Silicon Compounds
0
silicon nitride
QHB8T06IDK
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
395-410Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL125265
Pays : United States
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