Instruction of circulating endothelial progenitors in vitro towards specialized blood-brain barrier and arterial phenotypes

PLoS One. 2014 Jan 2;9(1):e84179. doi: 10.1371/journal.pone.0084179. eCollection 2014.

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.

Approach and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / cytology*
  • Arteries / metabolism*
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Blood-Brain Barrier / cytology*
  • Blood-Brain Barrier / metabolism*
  • Capillary Permeability
  • Cell Culture Techniques
  • Coculture Techniques
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Fetal Blood / cytology
  • Gene Expression Profiling
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Phenotype*
  • Rats
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcriptome
  • Veins / metabolism

Grant support

This work was supported by a grant by the National Research Agency (ANR, Barrier project, Fond unique d’investissement AAP7∶109-2024/R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.