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A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

  • Cecchelli R Blood Brain Barrier Laboratory, University of Artois, Lens, France.
  • Aday S CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal.
  • Sevin E Blood Brain Barrier Laboratory, University of Artois, Lens, France.
  • Almeida C CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), Coimbra, Portugal.
  • Culot M Blood Brain Barrier Laboratory, University of Artois, Lens, France.
  • Dehouck L Blood Brain Barrier Laboratory, University of Artois, Lens, France.
  • Coisne C Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • Engelhardt B Theodor Kocher Institute, University of Bern, Bern, Switzerland.
  • Dehouck MP Blood Brain Barrier Laboratory, University of Artois, Lens, France.
  • Ferreira L CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal.
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  • 2014-06-18
Published in:
  • PloS one. - 2014
Biomarkers
Blood-Brain Barrier
Capillary Permeability
Cell Adhesion Molecules
Cell Differentiation
Cells, Cultured
Coculture Techniques
Endothelial Cells
Endothelium, Vascular
Gene Expression
Hedgehog Proteins
Hematopoietic Stem Cells
Humans
Models, Biological
Pericytes
Reproducibility of Results
Wnt Signaling Pathway
English The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/156009
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