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https://hdl.handle.net/10316/92392
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 | 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. | URI: | https://hdl.handle.net/10316/92392 | 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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File | Description | Size | Format | |
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Almeida Stem Cell Reports.pdf | 19.93 MB | Adobe PDF | View/Open |
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