Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors
Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050121000310 |
| _version_ | 1819007085740818432 |
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| author | Maria Laggner Alfred Gugerell Dragan Copic Markus Jeitler Michael Springer Anja Peterbauer Christopher Kremslehner Manuel Filzwieser-Narzt Florian Gruber Sibylle Madlener Michael Erb Joachim Widder Wolfgang Lechner Dietmar Georg Michael Mildner Hendrik Jan Ankersmit |
| author_facet | Maria Laggner Alfred Gugerell Dragan Copic Markus Jeitler Michael Springer Anja Peterbauer Christopher Kremslehner Manuel Filzwieser-Narzt Florian Gruber Sibylle Madlener Michael Erb Joachim Widder Wolfgang Lechner Dietmar Georg Michael Mildner Hendrik Jan Ankersmit |
| author_sort | Maria Laggner |
| collection | DOAJ |
| description | Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine. |
| first_indexed | 2024-12-21T00:18:59Z |
| format | Article |
| id | doaj.art-76252835b5b848bfa2306b9f00468b98 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-12-21T00:18:59Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-76252835b5b848bfa2306b9f00468b982022-12-21T19:22:09ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012021-06-01211427Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factorsMaria Laggner0Alfred Gugerell1Dragan Copic2Markus Jeitler3Michael Springer4Anja Peterbauer5Christopher Kremslehner6Manuel Filzwieser-Narzt7Florian Gruber8Sibylle Madlener9Michael Erb10Joachim Widder11Wolfgang Lechner12Dietmar Georg13Michael Mildner14Hendrik Jan Ankersmit15Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria; Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria; Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria; Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, AustriaCore Facility Genomics, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria; Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, AustriaAustrian Red Cross Blood Transfusion Service of Upper Austria, 4020 Linz, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; Christian Doppler Laboratory for Biotechnology of Skin Aging, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; Christian Doppler Laboratory for Biotechnology of Skin Aging, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; Christian Doppler Laboratory for Biotechnology of Skin Aging, 1090 Vienna, AustriaMolecular Neuro-Oncology, Department of Pediatrics and Adolescent Medicine, and Institute of Neurology, Medical University of Vienna, 1090 Vienna, Austria; Comprehensive Cancer Center of the Medical University of Vienna, 1090 Vienna, AustriaSYNLAB Analytics and Services Switzerland AG, 4127 Birsfelden, SwitzerlandDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; Corresponding author: Michael Mildner, Department of Dermatology, Medical University of Vienna, Lazarettgasse 14, 1090 Vienna, Austria.Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria; Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, Austria; Corresponding author: Hendrik Jan Ankersmit, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.http://www.sciencedirect.com/science/article/pii/S2329050121000310regenerative medicinecell-free secretomesparacrine factorsbiological medicinal productsγ-irradiationelectron-irradiation |
| spellingShingle | Maria Laggner Alfred Gugerell Dragan Copic Markus Jeitler Michael Springer Anja Peterbauer Christopher Kremslehner Manuel Filzwieser-Narzt Florian Gruber Sibylle Madlener Michael Erb Joachim Widder Wolfgang Lechner Dietmar Georg Michael Mildner Hendrik Jan Ankersmit Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors Molecular Therapy: Methods & Clinical Development regenerative medicine cell-free secretomes paracrine factors biological medicinal products γ-irradiation electron-irradiation |
| title | Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors |
| title_full | Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors |
| title_fullStr | Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors |
| title_full_unstemmed | Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors |
| title_short | Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors |
| title_sort | comparing the efficacy of γ and electron irradiation of pbmcs to promote secretion of paracrine regenerative factors |
| topic | regenerative medicine cell-free secretomes paracrine factors biological medicinal products γ-irradiation electron-irradiation |
| url | http://www.sciencedirect.com/science/article/pii/S2329050121000310 |
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