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

Cecchelli, Romeo; Aday, Sezin; Sevin, Emmanuel; Almeida, Catarina; Culot, Maxime; Dehouck, Lucie; Coisne, Caroline Marie; Engelhardt, Britta; Dehouck, Marie-Pierre; Ferreira, Lino (2014). A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. PLoS ONE, 9(6), e99733. Public Library of Science 10.1371/journal.pone.0099733

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Coisne, Caroline Marie and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

07 Apr 2015 13:04

Last Modified:

08 Apr 2015 09:34

Publisher DOI:

10.1371/journal.pone.0099733

PubMed ID:

24936790

BORIS DOI:

10.7892/boris.66347

URI:

https://boris.unibe.ch/id/eprint/66347

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