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Wagner, Tanja; Traxler, Denise; Simader, Elisabeth; Beer, Lucian; Narzt, Marie-Sophie; Gruber, Florian; Madlener, Sibylle; Laggner, Maria; Erb, Michael; Vorstandlechner, Vera; Gugerell, Alfred; Radtke, Christine; Gnecchi, Massimiliano; Peterbauer, Anja; Gschwandtner, Maria; Tschachler, Erwin; Keibl, Claudia; Slezak, Paul; Ankersmit, Hendrik J.; Mildner, Michael

Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions

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  • Media type: E-Article
  • Title: Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions
  • Contributor: Wagner, Tanja; Traxler, Denise; Simader, Elisabeth; Beer, Lucian; Narzt, Marie-Sophie; Gruber, Florian; Madlener, Sibylle; Laggner, Maria; Erb, Michael; Vorstandlechner, Vera; Gugerell, Alfred; Radtke, Christine; Gnecchi, Massimiliano; Peterbauer, Anja; Gschwandtner, Maria; Tschachler, Erwin; Keibl, Claudia; Slezak, Paul; Ankersmit, Hendrik J.; Mildner, Michael
  • imprint: Springer Science and Business Media LLC, 2018
  • Published in: Scientific Reports
  • Language: English
  • DOI: 10.1038/s41598-018-36928-6
  • ISSN: 2045-2322
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Secretomes from various cell sources exert strong regenerative activities on numerous organs, including the skin. Although secretomes consist of many diverse components, a growing body of evidence suggests that small extracellular vesicles (EVs) account for their regenerative capacity. We previously demonstrated that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCs) exhibits wound healing capacity. Therefore, we sought to dissect the molecular composition of EVs present in the secretome and compared wound healing-related activities of these EVs to other subfractions of the secretome and the fully supplemented secretome (MNC<jats:sup>aposec</jats:sup>). Compared to EVs derived from non-irradiated PBMCs, γ-irradiation significantly increased the size and number and changed the composition of released EVs. Detailed characterization of the molecular components of EVs, <jats:italic>i.e</jats:italic>. miRNA, proteins, and lipids, derived from irradiated PBMCs revealed a strong association with regenerative processes. Reporter gene assays and aortic ring sprouting assays revealed diminished activity of the subfractions compared to MNC<jats:sup>aposec</jats:sup>. In addition, we showed that MNC<jats:sup>aposec</jats:sup> accelerated wound closure in a diabetic mouse model. Taken together, our results suggest that secretome-based wound healing represents a promising new therapeutic avenue, and strongly recommend using the complete secretome instead of purified subfractions, such as EVs, to exploit its full regenerative capacity.</jats:p>
  • Access State: Open Access