An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons

Fluids and Barriers of the CNS
Scott G CanfieldEric V Shusta

Abstract

Brain microvascular endothelial cells (BMECs) astrocytes, neurons, and pericytes form the neurovascular unit (NVU). Interactions with NVU cells endow BMECs with extremely tight barriers via the expression of tight junction proteins, a host of active efflux and nutrient transporters, and reduced transcellular transport. To recreate the BMEC-enhancing functions of NVU cells, we combined BMECs, astrocytes, neurons, and brain pericyte-like cells. BMECs, neurons, astrocytes, and brain like pericytes were differentiated from human induced pluripotent stem cells (iPSCs) and placed in a Transwell-type NVU model. BMECs were placed in co-culture with neurons, astrocytes, and/or pericytes alone or in varying combinations and critical barrier properties were monitored. Co-culture with pericytes followed by a mixture of neurons and astrocytes (1:3) induced the greatest barrier tightening in BMECs, supported by a significant increase in junctional localization of occludin. BMECs also expressed active P-glycoprotein (PGP) efflux transporters under baseline BMEC monoculture conditions and continued to express baseline active PGP efflux transporters regardless of co-culture conditions. Finally, brain-like pericyte co-culture significantly reduc...Continue Reading

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Citations

Apr 18, 2020·Molecular Autism·Aaron Gordon, Daniel H Geschwind
Jun 18, 2020·Pharmaceutics·Maria Inês TeixeiraDimitrios A Lamprou
Jun 24, 2020·Tissue Engineering. Part B, Reviews·Richard JeskeYan Li
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Mar 7, 2020·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
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Apr 24, 2020·Fluids and Barriers of the CNS·Michael J Workman, Clive N Svendsen
Apr 2, 2020·Fluids and Barriers of the CNS·Michelle A EricksonWilliam A Banks
Oct 21, 2020·Fluids and Barriers of the CNS·Ethan S LippmannEric V Shusta
Oct 31, 2020·Cellular and Molecular Neurobiology·Chengli LiuWei Wang
Nov 17, 2020·Tissue Barriers·Mehmet Kaya, Bulent Ahishali
Feb 23, 2021·Frontiers in Neuroscience·Nikolay SolovyevBernhard Michalke
Jul 17, 2020·Microvascular Research·Raleigh M LinvillePeter C Searson
May 1, 2021·Micromachines·Tiffany CameronKaren C Cheung
Sep 2, 2021·Annual Review of Biomedical Data Science·Jonathan Li, Ernest Fraenkel

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