Advancing human induced pluripotent stem cell-derived blood-brain barrier models for studying immune cell interactions.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_08BCD9D52C53
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Advancing human induced pluripotent stem cell-derived blood-brain barrier models for studying immune cell interactions.
Journal
FASEB journal
Author(s)
Nishihara H., Gastfriend B.D., Soldati S., Perriot S., Mathias A., Sano Y., Shimizu F., Gosselet F., Kanda T., Palecek S.P., Du Pasquier R., Shusta E.V., Engelhardt B.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Publication state
Published
Issued date
12/2020
Peer-reviewed
Oui
Volume
34
Number
12
Pages
16693-16715
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier (BBB) models established to date lack expression of key adhesion molecules involved in immune cell migration across the BBB in vivo. Here, we introduce the extended endothelial cell culture method (EECM), which differentiates hiPSC-derived endothelial progenitor cells to brain microvascular endothelial cell (BMEC)-like cells with good barrier properties and mature tight junctions. Importantly, EECM-BMEC-like cells exhibited constitutive cell surface expression of ICAM-1, ICAM-2, and E-selectin. Pro-inflammatory cytokine stimulation increased the cell surface expression of ICAM-1 and induced cell surface expression of P-selectin and VCAM-1. Co-culture of EECM-BMEC-like cells with hiPSC-derived smooth muscle-like cells or their conditioned medium further increased the induction of VCAM-1. Functional expression of endothelial ICAM-1 and VCAM-1 was confirmed by T-cell interaction with EECM-BMEC-like cells. Taken together, we introduce the first hiPSC-derived BBB model that displays an adhesion molecule phenotype that is suitable for the study of immune cell interactions.
Keywords
T-cell migration, VCAM-1, adhesion molecules, blood-brain barrier, human induced pluripotent stem cells
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2020 11:28
Last modification date
30/04/2021 7:08
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