Good news!
"Researchers have created a 3D model of the blood-brain barrier — a membrane that protects the brain from pathogens — entirely from human induced pluripotent stem cells. The model provides an alternative to rodent and in vitro models which fall short on translatability and hinder drug discovery. Stem cells are induced to become endothelial cells, astrocytes and pericytes or smooth muscle cells, which then develop into vessel-like tubes (pictured) mimicking the blood-brain barrier. Malfunctions of the barrier can cause neurodegenerative disorders and other health problems."
From the 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."
Nature Briefing: Translational Research
Fig. 2: Generation and characterization of a fully iPS-cell-derived human 3D BBB model to investigate neurovascular disorders. [what a busy figure]
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