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@ARTICLE{Fengler:164543,
      author       = {Fengler, Sven and Kurkowsky, Birgit and Kaushalya, Sanjeev
                      Kumar and Roth, Wera and Fava, Eugenio and Denner, Philip},
      title        = {{H}uman i{PSC}-derived brain endothelial microvessels in a
                      multi-well format enable permeability screens of
                      anti-inflammatory drugs.},
      journal      = {Biomaterials},
      volume       = {286},
      issn         = {0142-9612},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DZNE-2022-01092},
      pages        = {121525},
      year         = {2022},
      note         = {(CC BY-NC-ND)},
      abstract     = {Optimizing drug candidates for blood-brain barrier (BBB)
                      penetration remains one of the key challenges in drug
                      discovery to finally target brain disorders including
                      neurodegenerative diseases which do not have adequate
                      treatments so far. It has been difficult to establish
                      state-of-the-art stem cell derived in vitro models that
                      mimic physiological barrier properties including a 3D
                      microvasculature in a format that is scalable to screen
                      drugs for BBB penetration. To address this challenge, we
                      established human induced pluripotent stem cell
                      (iPSC)-derived brain endothelial microvessels in a
                      standardized and scalable multi-well plate format.
                      iPSC-derived brain microvascular endothelial cells (BMECs)
                      were supplemented with primary cell conditioned media and
                      grew to microvessels in 10 days. Produced microvessels show
                      typical BBB endothelial protein expression, tight-junctions
                      and polarized localization of efflux transporter.
                      Microvessels exhibited physiological relevant
                      trans-endothelial electrical resistance (TEER), were
                      leak-tight for 10 kDa dextran-Alexa 647 and strongly limited
                      the permeability of sodium fluorescein (NaF). Permeability
                      tests with reference compounds confirmed the suitability of
                      our model as platform to identify potential BBB penetrating
                      anti-inflammatory drugs. The here presented platform
                      recapitulates physiological properties and allows rapid
                      screening of BBB permeable anti-inflammatory compounds that
                      has been suggested as promising substances to cure so far
                      untreatable neurodegenerative diseases.},
      keywords     = {Anti-Inflammatory Agents: metabolism / Anti-Inflammatory
                      Agents: pharmacology / Blood-Brain Barrier: metabolism /
                      Brain: physiology / Cell Differentiation: physiology /
                      Cells, Cultured / Endothelial Cells: metabolism / Humans /
                      Induced Pluripotent Stem Cells: metabolism / Microvessels:
                      metabolism / Permeability / 3D microvessel (Other) /
                      Blood-brain barrier chip (Other) / Conditioned medium
                      (Other) / Drug permeability (Other) / High-content
                      microfluidic (Other) / Induced pluripotent stem cells
                      (Other)},
      cin          = {AG Fava 1 / LAT / LMF / AG Fava 2},
      ddc          = {570},
      cid          = {I:(DE-2719)1013016 / I:(DE-2719)1040190 /
                      I:(DE-2719)1040180 / I:(DE-2719)1040000},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35599022},
      doi          = {10.1016/j.biomaterials.2022.121525},
      url          = {https://pub.dzne.de/record/164543},
}