Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.
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.
Department of Chemical and Biological Engineering, University of Wisconsin–Madison, Madison, Wisconsin, USA.
Ethan S
ES
Lippmann
Samira M
SM
Azarin
Jennifer E
JE
Kay
Randy A
RA
Nessler
Hannah K
HK
Wilson
Abraham
A
Al-Ahmad
Sean P
SP
Palecek
Eric V
EV
Shusta
D001812:Blood-Brain Barrier / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin