Home > In process > A fully iPS-cell-derived 3D model of the human blood-brain barrier for exploring neurovascular disease mechanisms and therapeutic interventions. > print

001     285049
005     20260209105308.0
024 7 _ |a 10.1038/s41593-025-02123-w
|2 doi
024 7 _ |a pmid:41398476
|2 pmid
024 7 _ |a pmc:PMC12880921
|2 pmc
024 7 _ |a 1097-6256
|2 ISSN
024 7 _ |a 1546-1726
|2 ISSN
037 _ _ |a DZNE-2026-00173
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a González-Gallego, Judit
|0 0009-0005-0034-0595
|b 0
245 _ _ |a A fully iPS-cell-derived 3D model of the human blood-brain barrier for exploring neurovascular disease mechanisms and therapeutic interventions.
260 _ _ |a New York, NY
|c 2026
|b Nature America
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1770630256_24273
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
536 _ _ |a 351 - Brain Function (POF4-351)
|0 G:(DE-HGF)POF4-351
|c POF4-351
|f POF IV
|x 1
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 2
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Forkhead Transcription Factors
|2 NLM Chemicals
650 _ 2 |a Blood-Brain Barrier: physiology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: physiology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Forkhead Transcription Factors: genetics
|2 MeSH
650 _ 2 |a Endothelial Cells: physiology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Astrocytes: physiology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
700 1 _ |a Todorov-Völgyi, Katalin
|0 0009-0007-8073-9524
|b 1
700 1 _ |a Müller, Stephan A
|0 P:(DE-2719)2810938
|b 2
700 1 _ |a Antesberger, Sophie
|b 3
700 1 _ |a Todorov, Mihail Ivilinov
|0 0000-0002-8627-1260
|b 4
700 1 _ |a Malik, Rainer
|b 5
700 1 _ |a Grimalt-Mirada, Rita
|b 6
700 1 _ |a Gonçalves, Carolina Cardoso
|b 7
700 1 _ |a Schifferer, Martina
|0 P:(DE-2719)2812260
|b 8
700 1 _ |a Kislinger, Georg
|0 P:(DE-2719)9000614
|b 9
|u dzne
700 1 _ |a Weisheit, Isabel
|b 10
700 1 _ |a Lindner, Barbara
|b 11
700 1 _ |a Crusius, Dennis
|b 12
700 1 _ |a Kroeger, Joseph
|b 13
700 1 _ |a Borri, Mila
|0 0000-0002-6432-1888
|b 14
700 1 _ |a Erturk, Ali
|b 15
700 1 _ |a Nelson, Mark
|b 16
700 1 _ |a Misgeld, Thomas
|0 P:(DE-2719)2810727
|b 17
700 1 _ |a Lichtenthaler, Stefan F
|0 P:(DE-2719)2181459
|b 18
700 1 _ |a Dichgans, Martin
|0 P:(DE-2719)2000030
|b 19
700 1 _ |a Paquet, Dominik
|0 P:(DE-2719)2010112
|b 20
773 _ _ |a 10.1038/s41593-025-02123-w
|g Vol. 29, no. 2, p. 479 - 492
|0 PERI:(DE-600)1494955-6
|n 2
|p 479 - 492
|t Nature neuroscience
|v 29
|y 2026
|x 1097-6256
856 4 _ |u https://pub.dzne.de/record/285049/files/DZNE-2026-00173.pdf
|y Restricted
856 4 _ |u https://pub.dzne.de/record/285049/files/DZNE-2026-00173.pdf?subformat=pdfa
|x pdfa
|y Restricted
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)2810938
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 8
|6 P:(DE-2719)2812260
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 9
|6 P:(DE-2719)9000614
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 17
|6 P:(DE-2719)2810727
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 18
|6 P:(DE-2719)2181459
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 19
|6 P:(DE-2719)2000030
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-351
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Brain Function
|x 1
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 2
915 _ _ |a National-Konsortium
|0 StatID:(DE-HGF)0430
|2 StatID
|d 2025-11-07
|w ger
915 _ _ |a DEAL Nature
|0 StatID:(DE-HGF)3003
|2 StatID
|d 2025-11-07
|w ger
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-11-07
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-11-07
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NAT NEUROSCI : 2022
|d 2025-11-07
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2025-11-07
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2025-11-07
915 _ _ |a IF >= 25
|0 StatID:(DE-HGF)9925
|2 StatID
|b NAT NEUROSCI : 2022
|d 2025-11-07
920 1 _ |0 I:(DE-2719)1110006
|k AG Lichtenthaler
|l Neuroproteomics
|x 0
920 1 _ |0 I:(DE-2719)1110000-4
|k AG Misgeld
|l Neuronal Cell Biology
|x 1
920 1 _ |0 I:(DE-2719)5000022
|k AG Dichgans
|l Vascular Cognitive Impairment & Post-Stroke Dementia
|x 2
980 _ _ |a journal
980 _ _ |a EDITORS
980 _ _ |a VDBINPRINT
980 _ _ |a I:(DE-2719)1110006
980 _ _ |a I:(DE-2719)1110000-4
980 _ _ |a I:(DE-2719)5000022
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21