title: Generation of Brain Microvascular Endothelial-Like Cells from Human Induced Pluripotent Stem Cells by Co-Culture with C6 Glioma Cells.
abstract: The blood brain barrier (BBB) is formed by brain microvascular endothelial cells (BMECs) and tightly regulates the transport of molecules from blood to neural tissues. In vitro BBB models from human pluripotent stem cell (PSCs)-derived BMECs would be useful not only for the research on the BBB development and function but also for drug-screening for neurological diseases. However, little is known about the differentiation of human PSCs to BMECs. In the present study, human induced PSCs (iPSCs) were differentiated into endothelial cells (ECs), and further maturated to BMECs. Interestingly, C6 rat glioma cell-conditioned medium (C6CM), in addition to C6 co-culture, induced the differentiation of human iPSC-derived ECs (iPS-ECs) to BMEC-like cells, increase in the trans-endothelial electrical resistance, decreased in the dextran transport and up-regulation of gene expression of tight junction molecules in human iPS-ECs. Moreover, Wnt inhibitors attenuated the effects of C6CM. In summary, we have established a simple protocol of the generation of BMEC-like cells from human iPSCs, and have demonstrated that differentiation of iPS-ECs to BMEC-like cells is induced by C6CM-derived signals, including canonical Wnt signals.
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Minami
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Tashiro
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Okada
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Nobue
authors.initials: N
authors.lastname: Hirata
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; iPS Cell-based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; iPS Cell-based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
mesh_terms: D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D005910:Glioma / Q000473:pathology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D060449:Wnt Signaling Pathway
chemical_list: D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free