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Outgrowth endothelial cells form a functional cerebral barrier and restore its integrity after damage

Bayraktutan, Ulvi; Abdulkadir, RaisReskiawan; Alwjwaj, Mansour; Othman, OthmanAhmad; Rakkar, Kamini


RaisReskiawan Abdulkadir

Mansour Alwjwaj

OthmanAhmad Othman

Kamini Rakkar


Breakdown of blood-brain barrier, formed mainly by brain microvascular endothelial cells (BMECs), represents the major cause of mortality during early phases of ischemic strokes. Hence, discovery of novel agents that can effectively replace dead or dying endothelial cells to restore blood-brain barrier integrity is of paramount importance in stroke medicine. Although endothelial progenitor cells (EPCs) represent one such agents, their rarity in peripheral blood severely limits their adequate isolation and therapeutic use for acute ischemic stroke which necessitate their ex vivo expansion and generate early EPCs and outgrowth endothelial cells (OECs) as a result. Functional analyses of these cells, in the present study, demonstrated that only OECs endocytosed DiI-labelled acetylated low-density lipoprotein and formed tubules on matrigel, prominent endothelial cell and angiogenesis markers, respectively. Further analyses by flow cytometry demonstrated that OECs expressed specific markers for stemness (CD34), immaturity (CD133) and endothelial cells (CD31) but not for hematopoietic cells (CD45). Like BMECs, OECs established an equally tight in vitro model of human BBB with astrocytes and pericytes, suggesting their capacity to form tight junctions. Ischemic injury mimicked by concurrent deprivation of oxygen and glucose (4 hours) or deprivation of oxygen and glucose followed by reperfusion (20 hours) affected both barrier integrity and function in a similar fashion as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux, respectively. Wound scratch assays comparing the vasculoreparative capacity of cells revealed that, compared to BMECs, OECs possessed a greater proliferative and directional migratory capacity. In a triple culture model of BBB established with astrocytes, pericytes and BMEC, exogenous addition of OECs effectively repaired the damage induced on endothelial layer in serum-free conditions. Taken together, these data demonstrate that OECs may effectively home to the site of vascular injury and repair the damage to maintain (neuro)vascular homeostasis during or after a cerebral ischemic injury.


Bayraktutan, U., Abdulkadir, R., Alwjwaj, M., Othman, O., & Rakkar, K. (2020). Outgrowth endothelial cells form a functional cerebral barrier and restore its integrity after damage. Neural Regeneration Research, 15(6), 1071-1078.

Journal Article Type Article
Acceptance Date Oct 8, 2019
Online Publication Date Dec 13, 2019
Publication Date 2020
Deposit Date Dec 16, 2019
Journal Neural Regeneration Research
Print ISSN 1673-5374
Publisher Medknow Publications
Peer Reviewed Peer Reviewed
Volume 15
Issue 6
Pages 1071-1078
Keywords Developmental neuroscience
Public URL
Publisher URL;year=2020;volume=15;issue=6;spage=1071;epage=1078;aulast=Abdulkadir


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