Human Umbilical Cord Blood Endothelial Progenitor Cell-Derived Extracellular Vesicles Control Important Endothelial Cell Functions

Author:

Ben Fraj Sawssen123,Naserian Sina24ORCID,Lorenzini Bileyle2,Goulinet Sylvie2ORCID,Mauduit Philippe2ORCID,Uzan Georges2,Haouas Houda13

Affiliation:

1. National Institute of Applied Sciences and Technology (INSAT), Carthage University, Tunis 1080, Tunisia

2. INSERM UMR-S-MD 1197, Hôpital Paul Brousse, 94800 Villejuif, France

3. LR18ES40, Inflammation, Environment and Signalization Pathologies, Faculty of Medicine, University of Monastir, Monastir 5000, Tunisia

4. CellMedEx, 94100 Saint Maur Des Fossés, France

Abstract

Circulating endothelial progenitor cells (EPCs) play a pivotal role in the repair of diseases in which angiogenesis is required. Although they are a potentially valuable cell therapy tool, their clinical use remains limited due to suboptimal storage conditions and, especially, long-term immune rejection. EPC-derived extracellular vesicles (EPC-EVs) may be an alternative to EPCs given their key role in cell–cell communication and expression of the same parental markers. Here, we investigated the regenerative effects of umbilical cord blood (CB) EPC-EVs on CB-EPCs in vitro. After amplification, EPCs were cultured in a medium containing an EVs-depleted serum (EV-free medium). Then, EVs were isolated from the conditioned medium with tangential flow filtration (TFF). The regenerative effects of EVs on cells were investigated by analyzing cell migration, wound healing, and tube formation. We also analyzed their effects on endothelial cell inflammation and Nitric Oxide (NO) production. We showed that adding different doses of EPC-EVs on EPCs does not alter the basal expression of the endothelial cell markers nor change their proliferative potential and NO production level. Furthermore, we demonstrated that EPC-EVs, when used at a higher dose than the physiological dose, create a mild inflammatory condition that activates EPCs and boosts their regenerative features. Our results reveal for the first time that EPC-EVs, when used at a high dose, enhance EPC regenerative functions without altering their endothelial identity.

Funder

HC-Utique program

scholarship “bourse d’alternance” from the Tunisian Ministry of Higher Education and Scientific Research, Carthage University, Tunis, Tunisia

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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