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David Simpson, Eoin Brown, Christina O'Neill, Reinhold Medina, Jasenka Guduric-Fuchs; Manipulation of the MicroRNA Content of Endothelial Progenitor Cell-derived Extracellular Vesicles. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1586.
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The transfer of microRNAs between cells within membrane-bound extracellular vesicles has recently been confirmed as a novel mode of intercellular communication. We hypothesized that endothelial progenitor cells (EPCs) may employ this mechanism to communicate with endothelial cells during angiogenesis. Manipulation of the specific microRNAs transferred could potentially be used as an approach to modulate neovascularisation.
Vesicles released from EPCs isolated from human peripheral blood were collected by ultracentrifugation. The microRNA content of EPCs and their vesicles was analyzed by deep sequencing. Changes in mRNA expression in human microvascular endothelial cells (HMECs) following direct transfection with microRNA over-expression vectors were analysed by microarray. Expression of specific genes was measured by RT-qPCR.
The global profile of microRNAs within vesicles released from EPCs is distinct from that inside the cells. MicroRNAs highly enriched in extracellular vesicles included miR-486, miR-4792, miR-216a and miR-143. Vesicles from EPCs transfected with several vectors driving expression of microRNAs, including miR-146a and miR-451, were highly enriched in the over-expressed microRNA. When EPC-derived vesicles enriched with miR-146a were incubated with human microvascular endothelial cells they caused downregulation of miR-146a target genes.
Endogenous microRNAs are selectively packaged into extracellular vesicles. EPC vesicles can be manipulated to deliver specific microRNAs to endothelial cells. Such vesicles carrying candidate anti- or pro-angiogenic microRNAs may have therapeutic applications in multiple ocular diseases.
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