000164543 001__ 164543
000164543 005__ 20230915090552.0
000164543 0247_ $$2doi$$a10.1016/j.biomaterials.2022.121525
000164543 0247_ $$2pmid$$apmid:35599022
000164543 0247_ $$2ISSN$$a0142-9612
000164543 0247_ $$2ISSN$$a1878-5905
000164543 0247_ $$2altmetric$$aaltmetric:129708748
000164543 037__ $$aDZNE-2022-01092
000164543 041__ $$aEnglish
000164543 082__ $$a570
000164543 1001_ $$0P:(DE-2719)2812244$$aFengler, Sven$$b0$$eFirst author$$udzne
000164543 245__ $$aHuman iPSC-derived brain endothelial microvessels in a multi-well format enable permeability screens of anti-inflammatory drugs.
000164543 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2022
000164543 3367_ $$2DRIVER$$aarticle
000164543 3367_ $$2DataCite$$aOutput Types/Journal article
000164543 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1655291687_27749
000164543 3367_ $$2BibTeX$$aARTICLE
000164543 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000164543 3367_ $$00$$2EndNote$$aJournal Article
000164543 500__ $$a(CC BY-NC-ND)
000164543 520__ $$aOptimizing drug candidates for blood-brain barrier (BBB) penetration remains one of the key challenges in drug discovery to finally target brain disorders including neurodegenerative diseases which do not have adequate treatments so far. It has been difficult to establish state-of-the-art stem cell derived in vitro models that mimic physiological barrier properties including a 3D microvasculature in a format that is scalable to screen drugs for BBB penetration. To address this challenge, we established human induced pluripotent stem cell (iPSC)-derived brain endothelial microvessels in a standardized and scalable multi-well plate format. iPSC-derived brain microvascular endothelial cells (BMECs) were supplemented with primary cell conditioned media and grew to microvessels in 10 days. Produced microvessels show typical BBB endothelial protein expression, tight-junctions and polarized localization of efflux transporter. Microvessels exhibited physiological relevant trans-endothelial electrical resistance (TEER), were leak-tight for 10 kDa dextran-Alexa 647 and strongly limited the permeability of sodium fluorescein (NaF). Permeability tests with reference compounds confirmed the suitability of our model as platform to identify potential BBB penetrating anti-inflammatory drugs. The here presented platform recapitulates physiological properties and allows rapid screening of BBB permeable anti-inflammatory compounds that has been suggested as promising substances to cure so far untreatable neurodegenerative diseases.
000164543 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0
000164543 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000164543 650_7 $$2Other$$a3D microvessel
000164543 650_7 $$2Other$$aBlood-brain barrier chip
000164543 650_7 $$2Other$$aConditioned medium
000164543 650_7 $$2Other$$aDrug permeability
000164543 650_7 $$2Other$$aHigh-content microfluidic
000164543 650_7 $$2Other$$aInduced pluripotent stem cells
000164543 650_2 $$2MeSH$$aAnti-Inflammatory Agents: metabolism
000164543 650_2 $$2MeSH$$aAnti-Inflammatory Agents: pharmacology
000164543 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000164543 650_2 $$2MeSH$$aBrain: physiology
000164543 650_2 $$2MeSH$$aCell Differentiation: physiology
000164543 650_2 $$2MeSH$$aCells, Cultured
000164543 650_2 $$2MeSH$$aEndothelial Cells: metabolism
000164543 650_2 $$2MeSH$$aHumans
000164543 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: metabolism
000164543 650_2 $$2MeSH$$aMicrovessels: metabolism
000164543 650_2 $$2MeSH$$aPermeability
000164543 7001_ $$0P:(DE-2719)2810323$$aKurkowsky, Birgit$$b1$$udzne
000164543 7001_ $$0P:(DE-2719)2812833$$aKaushalya, Sanjeev Kumar$$b2$$udzne
000164543 7001_ $$0P:(DE-2719)2810635$$aRoth, Wera$$b3$$udzne
000164543 7001_ $$0P:(DE-2719)2159508$$aFava, Eugenio$$b4$$udzne
000164543 7001_ $$0P:(DE-2719)2810245$$aDenner, Philip$$b5$$eLast author$$udzne
000164543 773__ $$0PERI:(DE-600)2004010-6$$a10.1016/j.biomaterials.2022.121525$$gp. 121525 -$$p121525$$tBiomaterials$$v286$$x0142-9612$$y2022
000164543 8564_ $$uhttps://pub.dzne.de/record/164543/files/DZNE-2022-01092.pdf$$yOpenAccess
000164543 8564_ $$uhttps://pub.dzne.de/record/164543/files/DZNE-2022-01092.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000164543 909CO $$ooai:pub.dzne.de:164543$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812244$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810323$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812833$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810635$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2159508$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE
000164543 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810245$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000164543 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000164543 9141_ $$y2022
000164543 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-02-04
000164543 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-02-04
000164543 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000164543 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000164543 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-02-04
000164543 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-17$$wger
000164543 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOMATERIALS : 2021$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-17
000164543 915__ $$0StatID:(DE-HGF)9915$$2StatID$$aIF >= 15$$bBIOMATERIALS : 2021$$d2022-11-17
000164543 9201_ $$0I:(DE-2719)1013016$$kAG Fava 1$$lSystems Phenomics$$x0
000164543 9201_ $$0I:(DE-2719)1040190$$kLAT$$lLaboratory Automation Technologies (LAT)$$x1
000164543 9201_ $$0I:(DE-2719)1040180$$kLMF$$lLight Microscopy Facility (LMF)$$x2
000164543 9201_ $$0I:(DE-2719)1040000$$kAG Fava 2$$lLeitung Core Facilities$$x3
000164543 980__ $$ajournal
000164543 980__ $$aVDB
000164543 980__ $$aUNRESTRICTED
000164543 980__ $$aI:(DE-2719)1013016
000164543 980__ $$aI:(DE-2719)1040190
000164543 980__ $$aI:(DE-2719)1040180
000164543 980__ $$aI:(DE-2719)1040000
000164543 9801_ $$aFullTexts