title: Irradiation of Mesenchymal Stromal Cells With Low and High Doses of Alpha Particles Induces Senescence and/or Apoptosis.
abstract: The use of high-linear energy transfer charged particles is gaining attention as a medical tool because of the emission of radiations with an efficient cell-killing ability. Considerable interest has developed in the use of targeted alpha-particle therapy for the treatment of micrometastases. Moreover, the use of helium beams is gaining momentum, especially for treating pediatric tumors. We analyzed the effects of alpha particles on bone marrow mesenchymal stromal cells (MSCs), which have a subpopulation of stem cells capable of generating adipocytes, chondrocytes, and osteocytes. Further, these cells contribute toward maintenance of homeostasis in the body. MSCs were irradiated with low and high doses of alpha particles or X-rays and a comparative biological analysis was performed. At a low dose (40 mGy), alpha particles exhibited a limited negative effect on the biology of MSCs compared with X-rays. No significant perturbation of cell cycle was observed, and a minimal increase in apoptosis or senescence was detected. Self-renewal was preserved as revealed by the CFU assay. On the contrary, with 2000 mGy alpha particles, we observed adverse effects on the vitality, functionality, and stemness of MSCs. These results are the consequence of different proportion of cells targeted by alpha particles or X-rays and the quality of induced DNA damage. The present study suggests that radiotherapy with alpha particles may spare healthy stem cells more efficaciously than X-ray treatments, an observation that should be taken into consideration by physicians while planning irradiation of tumor areas close to stem cell niches, such as bone marrow. J. Cell. Biochem. 118: 2993-3002, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Experimental Medicine, Campania University "Luigi Vanvitelli", Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Alessio
authors.affiliation: Technology and Health Department, National Institute of Health, Rome, Italy.|National Institute of Nuclear Physics, Section Roma 1, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.affiliation: PSI Napoli Est - Laboratory UO, ASL Napoli 1 Centro, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Galano
authors.affiliation: PSI Napoli Est - Radiology UO, ASL Napoli 1 Centro, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Rosa
authors.affiliation: Technology and Health Department, National Institute of Health, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Anello
authors.affiliation: Institute of Agro-Environmental Biology and Forestry (IBAF), CNR, Naples, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.affiliation: Technology and Health Department, National Institute of Health, Rome, Italy.|National Institute of Nuclear Physics, Section Roma 1, Rome, Italy.
authors.forename: Maria Antonella
authors.initials: MA
authors.lastname: Tabocchini
authors.affiliation: Department of Experimental Medicine, Campania University "Luigi Vanvitelli", Naples, Italy.|Institute of Agro-Environmental Biology and Forestry (IBAF), CNR, Naples, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Umberto
authors.identifier: 0000-0003-0909-7403
authors.initials: U
authors.lastname: Galderisi
mesh_terms: D000512:Alpha Particles; D017209:Apoptosis / Q000528:radiation effects*; D016922:Cellular Senescence / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014965:X-Rays
keywords: APOPTOSIS; CANCER THERAPY; IRRADIATION; MESENCHYMAL STROMAL CELLS; SENESCENCE