Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors

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

doi:10.1016/j.omtm.2021.02.016

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors

Mol Ther Methods Clin Dev. 2021 Feb 24:21:14-27. doi: 10.1016/j.omtm.2021.02.016. eCollection 2021 Jun 11.

Authors

Maria Laggner^{1

2}, Alfred Gugerell^{1

2}, Dragan Copic^{1

2}, Markus Jeitler³, Michael Springer^{1

2}, Anja Peterbauer⁴, Christopher Kremslehner^{5

6}, Manuel Filzwieser-Narzt^{5

6}, Florian Gruber^{5

6}, Sibylle Madlener^{7

8}, Michael Erb⁹, Joachim Widder¹⁰, Wolfgang Lechner¹⁰, Dietmar Georg¹⁰, Michael Mildner⁵, Hendrik Jan Ankersmit^{1

2}

Affiliations

¹ Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria.
² Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, 1090 Vienna, Austria.
³ Core Facility Genomics, Medical University of Vienna, 1090 Vienna, Austria.
⁴ Austrian Red Cross Blood Transfusion Service of Upper Austria, 4020 Linz, Austria.
⁵ Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria.
⁶ Christian Doppler Laboratory for Biotechnology of Skin Aging, 1090 Vienna, Austria.
⁷ Molecular Neuro-Oncology, Department of Pediatrics and Adolescent Medicine, and Institute of Neurology, Medical University of Vienna, 1090 Vienna, Austria.
⁸ Comprehensive Cancer Center of the Medical University of Vienna, 1090 Vienna, Austria.
⁹ SYNLAB Analytics and Services Switzerland AG, 4127 Birsfelden, Switzerland.
¹⁰ Department of Radiation Oncology, Medical University of Vienna, 1090 Vienna, Austria.

Abstract

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.

Keywords: biological medicinal products; cell-free secretomes; electron-irradiation; paracrine factors; regenerative medicine; γ-irradiation; γ-irradiation replacement.