ArticleFluids and barriers of the CNS2019
An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons.
Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood-brain barrier.Nature biomedical engineering · 2025Pooled it
- Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- IFN-γ protects the human blood-brain barrier from Toxoplasma gondii-mediated dysfunction via CCL2 suppression.Journal of neuroinflammation · 2026Article
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.International journal of molecular sciences · 2026Review
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Substrate stiffness and cellular microenvironment regulate cell and junction mechanics in iPSC-derived brain microvascular endothelial cells.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial transplantation for delirium superimposed on dementia: from pathogenic mechanisms to clinical translation challenges.Frontiers in aging neuroscience · 2026Review
- Stem cell-derived brain-like endothelial cells to interrogateVirulence · 2025Article
- Sustaining Brain Youth by Neural Stem Cells: Physiological and Therapeutic Perspectives.Molecular neurobiology · 2025Review
- Ex Vivo Plasma Application on Human Brain Microvascular Endothelial-like Cells for Blood-Brain Barrier Modeling.International journal of molecular sciences · 2025Article
- Transcriptomic analysis of coxsackievirus B3 infection in induced pluripotent stem cell-derived brain-like endothelial cells.Journal of virology · 2025Article
- The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.Neurology international · 2025Review
- Lab Protocols for Coxsackievirus B3 Infection Using Brain-Like Endothelial Cells Derived from Induced-Pluripotent Human Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The role of astrocytes in ischemic stroke - mechanisms, functions and treatment.Frontiers in cell and developmental biology · 2025Review
- Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit.Fluids and barriers of the CNS · 2024Article
- Targeting the neurovascular unit: Therapeutic potential of traditional Chinese medicine for the treatment of stroke.Heliyon · 2024Review
- Review
- HumanTissue barriers · 2024Review
- Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain microvascular endothelial cells (BMECs) astrocytes, neurons, and pericytes form the neurovascular unit (NVU). Interactions with NVU cells endow BMECs with extremely tight barriers via the expression of tight junction proteins, a host of active efflux and nutrient transporters, and reduced transcellular transport. To recreate the BMEC-enhancing functions of NVU cells, we combined BMECs, astrocytes, neurons, and brain pericyte-like cells.
methodsBMECs, neurons, astrocytes, and brain like pericytes were differentiated from human induced pluripotent stem cells (iPSCs) and placed in a Transwell-type NVU model. BMECs were placed in co-culture with neurons, astrocytes, and/or pericytes alone or in varying combinations and critical barrier properties were monitored.
resultsCo-culture with pericytes followed by a mixture of neurons and astrocytes (1:3) induced the greatest barrier tightening in BMECs, supported by a significant increase in junctional localization of occludin. BMECs also expressed active P-glycoprotein (PGP) efflux transporters under baseline BMEC monoculture conditions and continued to express baseline active PGP efflux transporters regardless of co-culture conditions. Finally, brain-like pericyte co-culture significantly reduced the rate of non-specific transcytosis across BMECs.
conclusionsImportantly, each cell type in the NVU model was differentiated from the same donor iPSC source, yielding an isogenic model that could prove enabling for enhanced personalized modeling of the NVU in human health and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.