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PLoS One. 2014 Jun 17;9(6):e99733. doi: 10.1371/journal.pone.0099733. eCollection 2014.

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

Author information

1
Blood Brain Barrier Laboratory, University of Artois, Lens, France.
2
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.
3
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.
4
Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Abstract

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.

PMID:
24936790
PMCID:
PMC4061029
DOI:
10.1371/journal.pone.0099733
[Indexed for MEDLINE]
Free PMC Article

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