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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},
}