ArticleNature neuroscience2026
A fully iPS-cell-derived 3D model of the human blood-brain barrier for exploring neurovascular disease mechanisms and therapeutic interventions.
Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- A perfusable first-generation endometrial microvascular model to study human spiral artery remodeling in pregnancy.Lab on a chip · 2026Article
- Review
- Investigational New Drug-enabling studies in a human vessel-chip: Are we there yet?Bioengineering & translational medicine · 2026Review
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- Novel advanced patient-derivedFrontiers in neurologyReview
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Authors and funding
21 authors.
Funding
Abstract
Blood-brain barrier (BBB) integrity is critical for brain homeostasis, with malfunctions contributing to neurovascular and neurodegenerative disorders. Mechanistic studies on BBB function have been mostly conducted in rodent and in vitro models, which recapitulate some disease features, but have limited translatability to humans and pose challenges for drug discovery. Here we report on a fully human induced pluripotent stem (iPS)-cell-derived, microfluidic three-dimensional (3D) BBB model consisting of endothelial cells (ECs), mural cells and astrocytes. Our model expresses typical fate markers, forms a barrier in vessel-like tubes and enables perfusion, including with human blood. Deletion of FOXF2 in ECs, a major risk gene for cerebral small vessel disease, induced key features of BBB dysfunction, including compromised cell junction integrity and enhanced caveolae formation. Proteomic analysis revealed dysregulated endocytosis and cell junction pathways. Disease features phenocopied those seen in mice with EC-specific Foxf2 deficiency. Moreover, lipid-nanoparticle-based treatment with Foxf2 mRNA rescued BBB deficits, demonstrating the potential for drug development.
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Registered trials
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