First Insights into the Effect of Low-Dose X-Ray Irradiation in Adipose-Derived Stem Cells

Abstract

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1–2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

Theoretical derivation and clinical dose-response quantification of a unified multi-activation (UMA) model of cell survival from a logistic equation

“…To anticipate the skin reactions to low doses from diagnostic X-ray imaging, 24,25 the UMA model is applied to CSCs of human skin fibroblast cells by Weichselbaum et al 26 and stem cells by Schröder et al 27 as plots in Figure 3a and b , respectively. Skin intrinsic RS at zero dose defined by γ/ n of the skin cell lines are from 0.34 to 1.14 Gy −1 that are even higher than the initial RS of 0.075/Gy to the squamous cell carcinoma.…”

The Particle Radiobiology of Multipotent Mesenchymal Stromal Cells: A Key to Mitigating Radiation-Induced Tissue Toxicities in Cancer Treatment and Beyond?

“…In the study of Yang et al, the pro-survival effects of low-dose irradiation on human bone marrow MSCs were mediated via several proteins involved in cell cycle control such as Rb, cyclin E, CDK1, and CDC25B (83). Following these findings, there are considerations to use lowdose irradiation to support large scale expansion as well as therapeutic effects of MSCs (82,84). Unfortunately, to the best of our knowledge, no studies have reported effects of low-dose particle irradiation, especially protons, on the proliferation rate of MSCs.…”

“…It is important to consider that low-dose irradiation (≤ 0.1 Gy) has shown to have significantly different effects on MSCs and adipose-derived stem cells than higher radiation doses (24,82,83). Low dose irradiation was found to enhance proliferation and to increase the secretion of stem-cell factor (SCF) and GM-CSF, which may favor hematopoiesis (83).…”

Low-dose radiation therapy (LDRT) for COVID-19 and its deadlier variants

“…Another linear no-threshold modeling-based analysis forecasted the risk of secondary cancers to be approximately 1% after 15–20 years with the administration of a single 0.5 Gy dose to the thorax (Schrӧder et al 2019 ). Even if one accepts this likely overestimate, the risk of direct induced carcinogenic risk of LDRT (0.5–1.0 Gy) is still far below the risk of spontaneously occurring cancers (The 2007 recommendations of the international commission on radiological protection 2007 ).…”