Abstract
BackgroundSeveral studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis. The angiogenic mechanism has been ascribed to paracrine factors since these cells secrete a plenty of signal molecules and growth factors. Recently it has been suggested that besides soluble factors, extracellular vesicles (EVs) that include exosomes and microvesicles may play a major role in cell-to-cell communication. It has been shown that EVs are implicated in the angiogenic process.ResultsHerein we studied whether EVs released by ASCs may mediate the angiogenic activity of these cells. Our results demonstrated that ASC-derived EVs induced in vitro vessel-like structure formation by human microvascular endothelial cells (HMEC). EV-stimulated HMEC when injected subcutaneously within Matrigel in SCID mice formed vessels. Treatment of ASCs with platelet-derived growth factor (PDGF) stimulated the secretion of EVs, changed their protein composition and enhanced the angiogenic potential. At variance of EVs released in basal conditions, PDGF-EVs carried c-kit and SCF that played a role in angiogenesis as specific blocking antibodies inhibited in vitro vessel-like structure formation. The enhanced content of matrix metalloproteinases in PDGF-EVs may also account for their angiogenic activity.ConclusionsOur findings indicate that EVs released by ASCs may contribute to the ASC-induced angiogenesis and suggest that PDGF may trigger the release of EVs with an enhanced angiogenic potential.
Highlights
Several studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis
The expression did not change in different fractions of extracellular vesicles (EVs) or EVs obtained after stimulation with Platelet-derived growth factor (PDGF) with the exception of CD81 expression, which was increased in 100 k fraction of PDGF-EVs in respect to b-EVs (Table 1)
The results of the present study demonstrated that EVs released from ASCs stimulated in vitro and in vivo angiogenesis and that PDGF enhanced EV release and their angiogenic properties
Summary
Several studies demonstrate the role of adipose mesenchymal stem cells (ASCs) in angiogenesis. It has been suggested that besides soluble factors, extracellular vesicles (EVs) that include exosomes and microvesicles may play a major role in cell-to-cell communication. Almost all cell types release vesicles which include exosomes and microvesicles [1,2,3] Due to their heterogeneity it has been suggested to call them collectively extracellular vesicles (EVs). The adipose-derived stem cells (ASCs) are candidates for therapeutic application as autologous cells can be obtained by Platelet-derived growth factor (PDGF) is crucial for the selective expansion and recruitment of undifferentiated mesenchymal cells [14,15,16], favoring wound healing and vessel formation [17,18,19]. PDGF induces the migration and proliferation of mural progenitor cells during vascular development [14], stimulate endothelial cells [17] and induces mesenchymal cell transdifferentiation into vessel cells [20,21]
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