Gewählte Publikation:
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Neuro
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Kardio
Lipid
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Microb
Beer, L; Zimmermann, M; Mitterbauer, A; Ellinger, A; Gruber, F; Narzt, MS; Zellner, M; Gyöngyösi, M; Madlener, S; Simader, E; Gabriel, C; Mildner, M; Ankersmit, HJ.
Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration.
Sci Rep. 2015; 5(44):16662-16662
Doi: 10.1038/srep16662
[OPEN ACCESS]
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
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GABRIEL Christian
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- Abstract:
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We previously showed that, when peripheral blood mononuclear cells (PBMCs) were stressed with ionizing radiation, they released paracrine factors that showed regenerative capacity in vitro and in vivo. This study aimed to characterize the secretome of PBMCs and to investigate its biologically active components in vitro and vivo. Bioinformatics analysis revealed that irradiated PBMCs differentially expressed genes that encoded secreted proteins. These genes were primarily involved in (a) pro-angiogenic and regenerative pathways and (b) the generation of oxidized phospholipids with known pro-angiogenic and inflammation-modulating properties. Subsequently, in vitro assays showed that the exosome and protein fractions of irradiated and non-irradiated PBMC secretome were the major biological components that enhanced cell mobility; conversely, secreted lipids and microparticles had no effects. We tested a viral-cleared PBMC secretome, prepared according to good manufacturing practice (GMP), in a porcine model of closed chest, acute myocardial infarction. We found that the potency for preventing ventricular remodeling was similar with the GMP-compliant and experimentally-prepared PBMC secretomes. Our results indicate that irradiation modulates the release of proteins, lipid-mediators and extracellular vesicles from human PBMCs. In addition our findings implicate the use of secretome fractions as valuable material for the development of cell-free therapies in regenerative medicine.
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Acute Disease -
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Animals -
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Apoptosis - radiation effects
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Cell Line -
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Cell Movement -
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Cell-Derived Microparticles - metabolism
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Exosomes - metabolism
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Fibroblasts - cytology
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Fibroblasts - metabolism
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Humans -
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Leukocytes, Mononuclear - cytology
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Leukocytes, Mononuclear - metabolism
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Leukocytes, Mononuclear - radiation effects
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Lipid Peroxidation - radiation effects
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Lipids - analysis
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Male -
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Myocardial Infarction - metabolism
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Myocardial Infarction - pathology
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Myocardial Infarction - veterinary
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Oligonucleotide Array Sequence Analysis -
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Proteome - analysis
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Proteome - radiation effects
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Radiation, Ionizing -
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Regeneration - physiology
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Swine -
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Transcriptome - radiation effects
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Ventricular Remodeling -