title: Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes.
abstract: OBJECTIVE
  The vascular system is adapted to specific functions in different tissues and organs. Vascular endothelial cells are important elements of this adaptation, leading to the concept of 'specialized endothelial cells'. The phenotype of these cells is highly dependent on their specific microenvironment and when isolated and cultured, they lose their specific features after few passages, making models using such cells poorly predictive and irreproducible. We propose a new source of specialized endothelial cells based on cord blood circulating endothelial progenitors (EPCs). As prototype examples, we evaluated the capacity of EPCs to acquire properties characteristic of cerebral microvascular endothelial cells (blood-brain barrier (BBB)) or of arterial endothelial cells, in specific inducing culture conditions.
  
  
  RESULTS
  First, we demonstrated that EPC-derived endothelial cells (EPDCs) co-cultured with astrocytes acquired several BBB phenotypic characteristics, such as restricted paracellular diffusion of hydrophilic solutes and the expression of tight junction proteins. Second, we observed that culture of the same EPDCs in a high concentration of VEGF resulted, through activation of Notch signaling, in an increase of expression of most arterial endothelial markers.
  
  
  CONCLUSIONS
  We have thus demonstrated that in vitro culture of early passage human cord blood EPDCs under specific conditions can induce phenotypic changes towards BBB or arterial phenotypes, indicating that these EPDCs maintain enough plasticity to acquire characteristics of a variety of specialized phenotypes. We propose that this property of EPDCs might be exploited for producing specialized endothelial cells in culture to be used for drug testing and predictive in vitro assays.
authors.affiliation: Inserm U972, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Boyer-Di Ponio
authors.affiliation: ABCell-Bio, Paris, France.
authors.forename: Fida
authors.initials: F
authors.lastname: El-Ayoubi
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France ; Cnrs, UMR8104, Paris, France ; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Glacial
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France ; Cnrs, UMR8104, Paris, France ; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Kayathiri
authors.initials: K
authors.lastname: Ganeshamoorthy
authors.affiliation: Inserm U972, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Driancourt
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France ; Cnrs, UMR8104, Paris, France ; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Maeva
authors.initials: M
authors.lastname: Godet
authors.affiliation: VigiCell - Villejuif Biopark, Villejuif, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Perrière
authors.affiliation: Inserm U972, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Oriane
authors.initials: O
authors.lastname: Guillevic
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France ; Cnrs, UMR8104, Paris, France ; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre Olivier
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: Inserm U972, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology* / Q000378:metabolism*; D002199:Capillary Permeability; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome; D014680:Veins / Q000378:metabolism