https://www.ncbi.nlm.nih.gov/pubmed/26930059
Abstract
Neurovascular
inflammation is a major contributor to many neurological disorders, but
modeling these processes in vitro has proven to be difficult. Here, we
microengineered a three-dimensional (3D) model of the human blood-brain
barrier (BBB) within a microfluidic chip by creating a cylindrical
collagen gel containing a central hollow lumen inside a microchannel,
culturing primary human brain microvascular endothelial cells on the
gel's inner surface, and flowing medium through the lumen. Studies were
carried out with the engineered microvessel containing endothelium in
the presence or absence of either primary human brain pericytes beneath
the endothelium or primary human brain astrocytes within the surrounding
collagen gel to explore the ability of this simplified model to
identify distinct contributions of these supporting cells to the
neuroinflammatory response. This human 3D BBB-on-a-chip exhibited
barrier permeability similar to that observed in other in vitro BBB
models created with non-human cells, and when stimulated with the
inflammatory trigger, tumor necrosis factor-alpha (TNF-α), different
secretion profiles for granulocyte colony-stimulating factor (G-CSF) and
interleukin-6 (IL-6) were observed depending on the presence of
astrocytes or pericytes. Importantly, the levels of these responses
detected in the 3D BBB chip were significantly greater than when the
same cells were co-cultured in static Transwell plates. Thus, as G-CSF
and IL-6 have been reported to play important roles in neuroprotection
and neuroactivation in vivo, this 3D BBB chip potentially offers a new
method to study human neurovascular function and inflammation in vitro,
and to identify physiological contributions of individual cell types.
- PMID:
- 26930059
- PMCID:
- PMC4773137
- DOI:
- 10.1371/journal.pone.0150360
- [PubMed - indexed for MEDLINE]
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