Journal
STEM CELLS INTERNATIONAL
Volume 2016, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2016/1406304
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Funding
- British Heart Foundation [PG/14/16/30699, RE/13/6/30180]
- Cambridge Biomedical Research Centre
- British Heart Foundation [PG/14/16/30699, RG/13/4/30107, PG/10/74/28483] Funding Source: researchfish
- Medical Research Council [G0800142] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10086] Funding Source: researchfish
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Late outgrowth endothelial progenitor cells (LO-EPC) possess a high proliferative potential, differentiate into vascular endothelial cells (EC), and form networks, suggesting they play a role in vascular repair. However, due to their scarcity in the circulation there is a requirement for ex vivo expansion before they could provide a practical cell therapy and it is currently unclear if they would home and engraft to an injury site. Using an in vitro flow system we studied LO-EPC under simulated injury conditions including EC activation, ischaemia, disrupted EC integrity, and exposed basement membrane. Perfused LO-EPC adhered to discontinuous EC paracellularly at junctional regions between adjacent cells under shear stress 0.7 dyn/cm(2). The interaction was not adhesion molecule-dependent and not enhanced by EC activation. LO-EPC expressed high levels of the VE-Cadherin which may explain these findings. Ischaemia reperfusion injury decreased the interaction with LO-EPC due to cell retraction. LO-EPC interacted with exposed extracellular matrix (ECM) proteins, fibronectin and vitronectin. The interaction was mediated by integrins alpha 5 beta 3, alpha v beta 1, and alpha v beta 3. This study has demonstrated that an injured local environment presents sufficient adhesive signals to capture flow perfused LO-EPC in vitro and that LO-EPC have properties consistent with their potential role in vascular repair.
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