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- Title
Extracellular Vesicle-Derived microRNAs of Human Wharton's Jelly Mesenchymal Stromal Cells May Activate Endogenous VEGF-A to Promote Angiogenesis.
- Authors
Chinnici, Cinzia Maria; Iannolo, Gioacchin; Cittadini, Ettore; Carreca, Anna Paola; Nascari, David; Timoneri, Francesca; Bella, Mariangela Di; Cuscino, Nicola; Amico, Giandomenico; Carcione, Claudia; Conaldi, Pier Giulio; Alessandro, Riccardo
- Abstract
Despite low levels of vascular endothelial growth factor (VEGF)-A, the secretome of human Wharton's jelly (WJ) mesenchymal stromal cells (MSCs) effectively promoted proangiogenic responses in vitro, which were impaired upon the depletion of small (~140 nm) extracellular vesicles (EVs). The isolated EVs shared the low VEGF-A profile of the secretome and expressed five microRNAs, which were upregulated compared to fetal dermal MSC-derived EVs. These upregulated microRNAs exclusively targeted the VEGF-A gene within 54 Gene Ontology (GO) biological processes, 18 of which are associated with angiogenesis. Moreover, 15 microRNAs of WJ-MSC-derived EVs were highly expressed (Ct value ≤ 26) and exclusively targeted the thrombospondin 1 (THBS1) gene within 75 GO biological processes, 30 of which are associated with the regulation of tissue repair. The relationship between predicted microRNA target genes and WJ-MSC-derived EVs was shown by treating human umbilical-vein endothelial cells (HUVECs) with appropriate doses of EVs. The exposure of HUVECs to EVs for 72 h significantly enhanced the release of VEGF-A and THBS1 protein expression compared to untreated control cells. Finally, WJ-MSC-derived EVs stimulated in vitro tube formation along with the migration and proliferation of HUVECs. Our findings can contribute to a better understanding of the molecular mechanisms underlying the proangiogenic responses induced by human umbilical cord-derived MSCs, suggesting a key regulatory role for microRNAs delivered by EVs.
- Subjects
STROMAL cells; VASCULAR endothelial growth factors; MICRORNA; EXTRACELLULAR vesicles; NEOVASCULARIZATION
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 4, p2045
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22042045