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Title: Derivation of Brain Capillary-like Endothelial Cells from Human Pluripotent Stem Cell-Derived Endothelial Progenitor Cells
Authors: Praça, Catarina 
Rosa, Susana C. 
Sevin, Emmanuel
Cecchelli, Romeo
Dehouck, Marie-Pierre 
Ferreira, Lino S. 
Keywords: blood-brain barrier; brain capillary-like endothelial cells; extracellular matrices; induced pluripotent stem cells; in vitro model; soluble factors
Issue Date: 2019
Publisher: Elsevier
Project: LF would like to thank the funding obtained by the Portugal2020 project StrokeTherapy (Project reference: 3386), EC project ERA chair (ERA@UC, ref. 669088) and FCT projects (PTDC/DTP-FTO/2784/2014 and 02/SAICT/2017/029229). CP and SR would like to thank the fellowships of FCT (SFRH/BD/51678/2011; SFRH/BPD/79323/2011, respectively). 
Serial title, monograph or event: Stem Cell Reports
Volume: 13
Issue: 4
Abstract: The derivation of human brain capillary endothelial cells is of utmost importance for drug discovery programs focusing on diseases of the central nervous system. Here, we describe a two-step differentiation protocol to derive brain capillary-like endothelial cells from human pluripotent stem cells. The cells were initially differentiated into endothelial progenitor cells followed by specification into a brain capillary-like endothelial cell phenotype using a protocol that combined the induction, in a time-dependent manner, of VEGF, Wnt3a, and retinoic acid signaling pathways and the use of fibronectin as the extracellular matrix. The brain capillary-like endothelial cells displayed a permeability to lucifer yellow of 1 × 10-3 cm/min, a transendothelial electrical resistance value of 60 Ω cm2 and were able to generate a continuous monolayer of cells expressing ZO-1 and CLAUDIN-5 but moderate expression of P-glycoprotein. Further maturation of these cells required coculture with pericytes. The study presented here opens a new approach for the study of soluble and non-soluble factors in the specification of endothelial progenitor cells into brain capillary-like endothelial cells.
ISSN: 22136711
DOI: 10.1016/j.stemcr.2019.08.002
Rights: openAccess
Appears in Collections:UC Bibliotecas - Artigos em Revistas Internacionais

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