Fluids and Barriers of the CNS · 17 authors, 8 centres
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This study used a human iPSC-based in vitro model of the neurovascular unit to investigate how different brain cell types affect blood-brain barrier properties in a late-onset Alzheimer disease context. The central result is that the supportive effect of neural stem cells on barrier integrity is diminished under disease conditions, and various brain cell types exert unique, cell type-specific transcriptomic effects on brain capillary endothelial-like cells.
Researchers developed an in vitro model of the human neurovascular unit using isogenic induced pluripotent stem cells from a late-onset Alzheimer disease (LOAD) patient and a healthy control. The model included co-cultures of brain capillary endothelial-like cells with astrocytes, microglia-like cells, neural stem cells, and pericytes. Barrier integrity and transcriptomic profiles of the endothelial cells were assessed. The study found that co-cultures generally tightened the barrier and altered its transcriptomic profile under both healthy and disease conditions, but in vitro differentiation of the brain cell types was not affected by the LOAD background. A key finding was that the supportive effect of neural stem cells on barrier integrity was diminished in the LOAD model. The study suggests that each neurovascular cell type has a specific role in maintaining the blood-brain barrier that may be altered in LOAD.
