Membrane vesicles mediate pro-angiogenic activity of equine adipose-derived mesenchymal stromal cells

Abstract Multipotent mesenchymal stromal cells (MSCs) have attracted a great deal of interest, due to several distinctive features, including the ability to migrate to damaged tissue and to participate in tissue regeneration. There is increasing evidence that membrane vesicles (MVs), comprising exosomes and shedding vesicles, represent a key component, responsible for many of the paracrine effects of MSCs. The aim of the present study was to establish whether equine adipose-derived MSCs (E-AdMSCs) produce MVs that are capable of influencing angiogenesis, a key step in tissue regeneration. A morphological study was performed using MSC monolayers, prepared for transmission and scanning electron microscopy and on ultracentrifuged MSC supernatants, to identify production of MVs. The ability of MVs to influence angiogenesis was evaluated by means of the rat aortic ring and scratch assays. The results demonstrated that MVs, constitutively produced by E-AdMSCs, are involved in intercellular communication with endothelial cells, stimulating angiogenesis. Although many questions remain regarding their formation, delivery, content and mechanism of action, the present study supports the concept that MVs released by MSCs have the potential to be exploited as a therapeutic tool for regenerative medicine.