Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Apr 22;17(1):30.
doi: 10.1186/s12987-020-00191-7.

Recent advances in human iPSC-derived models of the blood-brain barrier

Michael J Workman  1 , Clive N Svendsen  2
Affiliations
Review

Recent advances in human iPSC-derived models of the blood-brain barrier

Michael J Workman et al. Fluids Barriers CNS. .

Abstract

The blood-brain barrier (BBB) is a critical component of the central nervous system that protects neurons and other cells of the brain parenchyma from potentially harmful substances found in peripheral circulation. Gaining a thorough understanding of the development and function of the human BBB has been hindered by a lack of relevant models given significant species differences and limited access to in vivo tissue. However, advances in induced pluripotent stem cell (iPSC) and organ-chip technologies now allow us to improve our knowledge of the human BBB in both health and disease. This review focuses on the recent progress in modeling the BBB in vitro using human iPSCs.

Keywords: Blood–brain barrier; Brain microvascular endothelial cells; Disease modeling; Human iPSC; Induced pluripotent stem cells; Organ-chip systems.

PubMed Disclaimer

Conflict of interest statement

Cedars-Sinai owns a minority stock interest in Emulate, a company that produces microfluidic organ-chips. An officer of Cedars-Sinai also serves on Emulate’s Board of Directors. Emulate provided no financial support for this manuscript.

Figures

Fig. 1
Fig. 1
Overview of modeling the blood–brain barrier using induced pluripotent stem cells
Fig. 2
Fig. 2
Schematic of differentiation protocols for deriving brain microvascular endothelial cells from induced pluripotent stem cells and main assay readouts for assessing BMEC phenotype. Main advancements from previous protocols are bolded. bFGF basic fibroblast growth factor, MEF mouse embryonic fibroblast, KOSR knockout serum replacement, l-glutl-glutamine, β-ME β-mercaptoethanol, ECSFM endothelial cell serum free media, PDS platelet-poor plasma derived serum, VEGF vascular endothelial growth factor, TEER transendothelial electrical resistance, ICC immunocytochemistry, ETA efflux transporter activity, FC flow cytometry, TEM transmission electron microscopy, RT-PCR reverse transcription polymerase chain reaction, qPCR quantitative polymerase chain reaction
Fig. 3
Fig. 3
a Principal component analysis of published RNA-sequencing data comparing transcriptomes of human iPSC-derived brain microvascular endothelial cells (iBMECs), immortalized BMEC cell lines, and immunopanned brain endothelial cells (BECs) from post-mortem samples. The first principal component (PC1), representing the largest proportion of explained variance, separates iPSC-derived from in vivo-sourced brain endothelial cells. b Gene ontology (GO) enrichment using the top 400 genes driving the separation of samples along PC1 reveal that pathways associated with immune signaling and angiogenesis are upregulated in immunopanned BECs and immortalized cell lines. c Conversely, iPSC-derived BMECs show upregulation of terms associated with cell proliferation, patterning, and extracellular matrix interaction
See this image and copyright information in PMC

References

    1. Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and Dysfunction of the blood–brain barrier. Cell. 2015;163:1064–1078. doi: 10.1016/j.cell.2015.10.067. - DOI - PMC - PubMed
    1. Syvänen S, Lindhe Ö, Palner M, Kornum BR, Rahman O, Långström B, et al. Species differences in blood–brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport. Drug Metab Dispos. 2009;37:635–643. doi: 10.1124/dmd.108.024745. - DOI - PubMed
    1. Warren MS, Zerangue N, Woodford K, Roberts LM, Tate EH, Feng B, et al. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol Res. 2009;59:404–413. doi: 10.1016/j.phrs.2009.02.007. - DOI - PubMed
    1. Shawahna R, Uchida Y, Declèves X, Ohtsuki S, Yousif S, Dauchy S, et al. Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Mol Pharm. 2011;8:1332–1341. doi: 10.1021/mp200129p. - DOI - PubMed
    1. Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C, Suzuki T, Kamiie J, et al. Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors. J Neurochem. 2011;117:333–345. doi: 10.1111/j.1471-4159.2011.07208.x. - DOI - PubMed

LinkOut - more resources