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Derivation of Brain Capillary-like Endothelial Cells from Human Pluripotent Stem Cell-Derived Endothelial Progenitor Cells

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.
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https://hal-univ-artois.archives-ouvertes.fr/hal-02505491
Contributor : Virginie Justin-Labonne <>
Submitted on : Wednesday, March 11, 2020 - 3:18:53 PM
Last modification on : Wednesday, March 25, 2020 - 3:43:18 PM

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Praça Catarina, Rosa Susana, Emmanuel Sevin, Romeo Cecchelli, Marie-Pierre Dehouck, et al.. Derivation of Brain Capillary-like Endothelial Cells from Human Pluripotent Stem Cell-Derived Endothelial Progenitor Cells. Stem Cell Reports, Elsevier, 2019, 13 (4), pp.599-611. ⟨10.1016/j.stemcr.2019.08.002⟩. ⟨hal-02505491⟩

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