Endothelial Cell-Derived Extracellular Vesicles Induce Pro-Angiogenic Responses in Mesenchymal Stem Cells

Abstract

Angiogenesis is a central component of vital biological processes such aswound healing, tissue nourishment, and development. Therefore, angio-genic activities are precisely maintained with secreted factors such asangiopoietin-1 (Ang1), fibroblast growth factor (FGF), and vascular endo-thelial growth factor (VEGF). As an element of intracellular communica-tion, extracellular vesicles (EVs)—particularly EVs of vascular origin—could have key functions in maintaining angiogenesis. However, the func-tions of EVs in the control of angiogenesis have not been fully studied. Inthis study, human umbilical vein endothelial cell line (HUVEC)-derivedsmall EVs (<200 nm; HU-sEVs) were investigated as a potential pro-angiogenic agent. Treating mesenchymal stem cells (MSCs) and matureHUVEC cells with HU-sEVs induced their tube formation under in vitroconditions and significantly increased the expression of angiogenesis-relatedgenes, such as Ang1, VEGF, Flk-1 (VEGF receptor 2), Flt-1 (VEGF recep-tor 1), and vWF (von Willebrand Factor), in a dose-dependent manner.These results indicate that HU-sEVs take part in angiogenesis activities inphysiological systems, and suggest endothelial EVs as a potential therapeu-tic candidate for the treatment of angiogenesis-related diseases.