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@ARTICLE{GonzlezGallego:285049,
      author       = {González-Gallego, Judit and Todorov-Völgyi, Katalin and
                      Müller, Stephan A and Antesberger, Sophie and Todorov,
                      Mihail Ivilinov and Malik, Rainer and Grimalt-Mirada, Rita
                      and Gonçalves, Carolina Cardoso and Schifferer, Martina and
                      Kislinger, Georg and Weisheit, Isabel and Lindner, Barbara
                      and Crusius, Dennis and Kroeger, Joseph and Borri, Mila and
                      Erturk, Ali and Nelson, Mark and Misgeld, Thomas and
                      Lichtenthaler, Stefan F and Dichgans, Martin and Paquet,
                      Dominik},
      title        = {{A} fully i{PS}-cell-derived 3{D} model of the human
                      blood-brain barrier for exploring neurovascular disease
                      mechanisms and therapeutic interventions.},
      journal      = {Nature neuroscience},
      volume       = {29},
      number       = {2},
      issn         = {1097-6256},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DZNE-2026-00173},
      pages        = {479 - 492},
      year         = {2026},
      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.},
      keywords     = {Blood-Brain Barrier: physiology / Humans / Induced
                      Pluripotent Stem Cells: physiology / Animals / Forkhead
                      Transcription Factors: genetics / Endothelial Cells:
                      physiology / Mice / Astrocytes: physiology / Cells, Cultured
                      / Forkhead Transcription Factors (NLM Chemicals)},
      cin          = {AG Lichtenthaler / AG Misgeld / AG Dichgans},
      ddc          = {610},
      cid          = {I:(DE-2719)1110006 / I:(DE-2719)1110000-4 /
                      I:(DE-2719)5000022},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
                      (POF4-351) / 353 - Clinical and Health Care Research
                      (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351 /
                      G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41398476},
      pmc          = {pmc:PMC12880921},
      doi          = {10.1038/s41593-025-02123-w},
      url          = {https://pub.dzne.de/record/285049},
}