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.

Bone marrow-derived mesenchymal stromal cells promote colorectal cancer cell death under low-dose irradiation

“…However, in the present study, the effect was not significant. It might be owing to the effect becoming impaired when secretomes were collected from senescent cells previously in contact with cancer cells as reported before (Özcan et al , 2015; Alessio et al , 2017).…”

In vitro expansion affects the response of human bone marrow stromal cells to irradiation

“…A significant difference in apoptosis but not senescence was observed between the P6 and P10 BMSCs after irradiation. However, BMSCs were shown to be prone to senescence rather than apoptosis after exposure to a low radiation dose in previous studies [35, 36]. Generally, BMSCs at late passages should be more resistant to apoptosis since they should have a higher percentage of senescent cells.…”

Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

“…concerning the direct damage of irradiation to biological function in osteocytes, irradiation can markedly inhibit the viability and proliferation of osteocytes, which ultimately leads to a decreased number of osteocytes in a dose-dependent manner. Although a high dose of radiation tends to induce more apoptosis and necrosis, previous research had demonstrated that the initial apoptotic cells tend to die rapidly, and the majority of surviving cells maintain senescence (46)(47)(48). Given these evidences, at 5 days after radiation a small number of apoptosis or necrosis osteocytes were inevitably mixed into exiting populations, while the majority of surviving cells maintain senescence.…”