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Sci Rep. 2018 Dec 4;8(1):17458. doi: 10.1038/s41598-018-36143-3.

PDGF enhances the protective effect of adipose stem cell-derived extracellular vesicles in a model of acute hindlimb ischemia.

Author information

1
Department of Medical Sciences, University of Turin, Turin, Italy. tatiana.lopatina@unito.it.
2
Department of Medical Sciences, University of Turin, Turin, Italy.
3
2i3T, Società per La Gestione Dell'incubatore Di Imprese e Per Il Trasferimento Tecnologico Dell'Università degli Studi di Torino, Scarl., Molecular Biotechnology Center (MBC), Turin, Italy.
4
Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1550 Orleans street, Rm 5M06, CRBII, Baltimore, MD, 21231, United States of America.
5
General Surgery 2U, Liver Transplantation Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.

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.

PMID:
30514962
DOI:
10.1038/s41598-018-36143-3
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