Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.

Lippmann ES, Azarin SM, Kay JE, Nessler RA, Wilson HK, Al-Ahmad A, Palecek SP, Shusta EV
Nat Biotechnol. 2012 30 (8): 783-91

PMID: 22729031 · PMCID: PMC3467331 · DOI:10.1038/nbt.2247

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 cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.

MeSH Terms (14)

beta Catenin Blood-Brain Barrier Cell Differentiation Cell Line Cell Separation Coculture Techniques Endothelial Cells Endothelium, Vascular Humans Neurons Phenotype Pluripotent Stem Cells Signal Transduction Wnt Proteins

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