title: Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
authors.forename: Lucian
authors.initials: L
authors.lastname: Beer
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mitterbauer
authors.affiliation: Department of Cell Biology and Ultrastructure Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.
authors.forename: Adolf
authors.initials: A
authors.lastname: Ellinger
authors.affiliation: Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Biotechnology of Skin Aging, Medical, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Gruber
authors.affiliation: Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Biotechnology of Skin Aging, Medical, Austria.
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Narzt
authors.affiliation: Centre of Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Zellner
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics and Adolescent Medicine and Institute of Neurology, Medical University of Vienna, Austria.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Madlener
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Simader
authors.affiliation: Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Department of Dermatology, Research Division of Biology and Pathobiology of the Skin, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.affiliation: Department of Thoracic Surgery, Medical University of Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002460:Cell Line; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000528:radiation effects; D008055:Lipids / Q000032:analysis; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000032:analysis* / Q000528:radiation effects; D011839:Radiation, Ionizing; D012038:Regeneration / Q000502:physiology; D013552:Swine; D059467:Transcriptome / Q000528:radiation effects; D020257:Ventricular Remodeling
chemical_list: D008055:Lipids; D020543:Proteome