Home > Publications Database > Human iPSC-derived brain endothelial microvessels in a multi-well format enable permeability screens of anti-inflammatory drugs. > print

001     164543
005     20230915090552.0
024 7 _ |a 10.1016/j.biomaterials.2022.121525
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024 7 _ |a 0142-9612
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024 7 _ |a 1878-5905
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037 _ _ |a DZNE-2022-01092
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Fengler, Sven
|0 P:(DE-2719)2812244
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245 _ _ |a Human iPSC-derived brain endothelial microvessels in a multi-well format enable permeability screens of anti-inflammatory drugs.
260 _ _ |a Amsterdam [u.a.]
|c 2022
|b Elsevier Science
336 7 _ |a article
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500 _ _ |a (CC BY-NC-ND)
520 _ _ |a 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.
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650 _ 7 |a 3D microvessel
|2 Other
650 _ 7 |a Blood-brain barrier chip
|2 Other
650 _ 7 |a Conditioned medium
|2 Other
650 _ 7 |a Drug permeability
|2 Other
650 _ 7 |a High-content microfluidic
|2 Other
650 _ 7 |a Induced pluripotent stem cells
|2 Other
650 _ 2 |a Anti-Inflammatory Agents: metabolism
|2 MeSH
650 _ 2 |a Anti-Inflammatory Agents: pharmacology
|2 MeSH
650 _ 2 |a Blood-Brain Barrier: metabolism
|2 MeSH
650 _ 2 |a Brain: physiology
|2 MeSH
650 _ 2 |a Cell Differentiation: physiology
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Endothelial Cells: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Microvessels: metabolism
|2 MeSH
650 _ 2 |a Permeability
|2 MeSH
700 1 _ |a Kurkowsky, Birgit
|0 P:(DE-2719)2810323
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700 1 _ |a Kaushalya, Sanjeev Kumar
|0 P:(DE-2719)2812833
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700 1 _ |a Roth, Wera
|0 P:(DE-2719)2810635
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700 1 _ |a Fava, Eugenio
|0 P:(DE-2719)2159508
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700 1 _ |a Denner, Philip
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773 _ _ |a 10.1016/j.biomaterials.2022.121525
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|t Biomaterials
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