A hydrogel model of the human blood-brain barrier using differentiated stem cells.

Autor: Nandita Rahatekar Singh, Radka Gromnicova, Andreas Brachner, Igor Kraev, Ignacio A Romero, Winfried Neuhaus, David Male
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: PLoS ONE, Vol 18, Iss 4, p e0283954 (2023)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0283954
Popis: An in vitro model of the human blood-brain barrier was developed, based on a collagen hydrogel containing astrocytes, overlaid with a monolayer of endothelium, differentiated from human induced pluripotent stem cells (hiPSCs). The model was set up in transwell filters allowing sampling from apical and basal compartments. The endothelial monolayer had transendothelial electrical resistance (TEER) values >700Ω.cm2 and expressed tight-junction markers, including claudin-5. After differentiation of hiPSCs the endothelial-like cells expressed VE-cadherin (CDH5) and von-Willebrand factor (VWF) as determined by immunofluorescence. However, electron microscopy indicated that at set-up (day 8 of differentiation), the endothelial-like cells still retained some features of the stem cells, and appeared immature, in comparison with primary brain endothelium or brain endothelium in vivo. Monitoring showed that the TEER declined gradually over 10 days, and transport studies were best carried out in a time window 24-72hrs after establishment of the model. Transport studies indicated low permeability to paracellular tracers and functional activity of P-glycoprotein (ABCB1) and active transcytosis of polypeptides via the transferrin receptor (TFR1).
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje