Abstract
We previously have shown that platelet-derived growth factor (PDGF) modulates the biological activity of extracellular vesicles released by adipose-derived mesenchymal stem cells (ASC-EVs). ASC-EVs may interact with blood and vessel cells by transferring proteins and nucleic acids and regulate their functions. In this study, we investigated immunomodulatory activity and protection from acute hindlimb ischemia of EVs released by PDGF-stimulated ASC (PDGF-EVs). PDGF treatment of ASC changed protein and RNA composition of released EVs by enhancing the expression of anti-inflammatory and immunomodulatory factors. In vitro, control EVs (cEVs) derived from non-stimulated ASC increased the secretion of both the IL-1b, IL-17, IFNγ, TNFα pro-inflammatory factors and the IL-10 anti-inflammatory factor, and enhanced the in vitro peripheral blood mononuclear cell (PBMC) adhesion on endothelium. In contrast, PDGF-EVs enhanced IL-10 secretion and induced TGF-β1 secretion by PBMC. Moreover, PDGF-EVs stimulated the formation of T regulatory cells. In vivo, PDGF-EVs protected muscle tissue from acute ischemia, reduced infiltration of inflammatory cells and increased T regulatory cell infiltration in respect to cEVs. Our results suggest that PDGF-EVs are enriched in anti-inflammatory and immunomodulatory factors and induced in PBMC an enhanced production of IL-10 and TGF-β1 resulting in protection of muscle from acute ischemia in vivo.
Highlights
Extracellular vesicles (EVs) are intercellular shuttles that were found in almost all biological liquids, such as saliva, urine, liquor, amniotic liquid, peritoneal fluid, and plasma
We investigated the effects of platelet-derived growth factor (PDGF)-EVs and control EVs (cEVs) on injured muscles using a model of acute hindlimb ischemia in mice
(90 nm) and morphology between cEVs and PDGF-EVs according to electron microscopy and nanoparticle tracking analysis (NTA) (Fig. 1a–d)
Summary
Extracellular vesicles (EVs) are intercellular shuttles that were found in almost all biological liquids, such as saliva, urine, liquor, amniotic liquid, peritoneal fluid, and plasma. EVs contain a specific set of lipids, proteins, and nucleic acids and can regulate the cell function and gene expression of the recipient cells[1,2,3] Vessel cells, such as endothelial cells, smooth muscle cells, or mesenchymal stem cells, release their EVs in the bloodstream, where they interact with blood cells. PDGF plays an essential role in angiogenesis and tissue regeneration[6] It is secreted either by platelets during vessel injury or by other cells, such as mesenchymal or endothelial cells[7]. In this study aimed to define the effect of ASC-derived EVs, released in response to PDGF stimulation (PDGF-EVs), in tissue regeneration and inflammation For this purpose, we compared the in vitro effect of control EVs (cEVs) and PDGF-EVs on peripheral blood mononuclear cells (PBMC). We investigated the effects of PDGF-EVs and cEVs on injured muscles using a model of acute hindlimb ischemia in mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
