title: Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential.
abstract: BACKGROUND
  Several 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.
  
  
  RESULTS
  Herein 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lopatina
authors.forename: Stefania
authors.initials: S
authors.lastname: Bruno
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.forename: Natalia
authors.initials: N
authors.lastname: Kalinina
authors.forename: Massimo
authors.initials: M
authors.lastname: Porta
authors.affiliation: Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, Corso Dogliotti 14, 10126, Torino, Italy. giovanni.camussi@unito.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D055806:Microvessels / Q000166:cytology; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*
chemical_list: D010982:Platelet-Derived Growth Factor
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