Abstract
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 (MNCaposec). 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, i.e. 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 MNCaposec. In addition, we showed that MNCaposec 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.
| Original language | English |
|---|---|
| Article number | 18016 |
| Journal | Scientific Reports |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2018 |
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Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions. / 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.
In: Scientific Reports, Vol. 8, No. 1, 18016, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions
AU - Wagner, Tanja
AU - Traxler, Denise
AU - Simader, Elisabeth
AU - Beer, Lucian
AU - Narzt, Marie Sophie
AU - Gruber, Florian
AU - Madlener, Sibylle
AU - Laggner, Maria
AU - Erb, Michael
AU - Vorstandlechner, Vera
AU - Gugerell, Alfred
AU - Radtke, Christine
AU - Gnecchi, Massimiliano
AU - Peterbauer, Anja
AU - Gschwandtner, Maria
AU - Tschachler, Erwin
AU - Keibl, Claudia
AU - Slezak, Paul
AU - Ankersmit, Hendrik J.
AU - Mildner, Michael
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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 (MNCaposec). 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, i.e. 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 MNCaposec. In addition, we showed that MNCaposec 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.
AB - 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 (MNCaposec). 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, i.e. 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 MNCaposec. In addition, we showed that MNCaposec 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85058843190&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-36928-6
DO - 10.1038/s41598-018-36928-6
M3 - Article
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 18016
ER -