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Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
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Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
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Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
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Journal Article
Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells
2012
Overview
Lippmann
et al
. present a protocol for differentiating human pluripotent stem cells into blood-brain barrier endothelial cells. The cells should be useful for studying this endothelial barrier, including screening for drugs that can cross from the blood to the brain.
The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm
2
), and they possess molecular permeability that correlates well with
in vivo
rodent blood-brain transfer coefficients.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 631/61
/ Biological and medical sciences
/ Biomedical Engineering/Biotechnology
/ Blood-Brain Barrier - cytology
/ Cell Differentiation - physiology
/ Coculture Techniques - methods
/ Diseases
/ Endothelial Cells - cytology
/ Endothelium, Vascular - cytology
/ Fundamental and applied biological sciences. Psychology
/ Health
/ Health. Pharmaceutical industry
/ Humans
/ Industrial applications and implications. Economical aspects
/ Pluripotent Stem Cells - cytology
/ Rodents
