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

Annemarie Schröder,Katrin Manda,Guido Hildebrandt,Stephan Kriesen

doi:10.3390/ijms20236075

Annemarie Schröder, Katrin Manda + Show 2 more

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https://doi.org/10.3390/ijms20236075

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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.

Highlights

In Germany, low-dose radiation therapy (LD-RT) is an approved and commonly used option in the treatment of degenerative bone and inflammatory diseases [1], such as heel spur and osteoarthritis [2,3,4]
Liang et al (2016) and Truong et al (2018) confirmed those trends in fibroblasts and lung cancer cell lines later on [16,17]. Those findings lead to an important question for scientists in the field of regenerative medicine: Could we induce the proliferation of mesenchymal stem cells by LD-RT below 0.1 Gy to enhance the success of several regenerative therapies? Liang et al (2011) and Yang et al (2017) were the first who detected proliferation stimulating effects in human and rat bone-marrow stem cells (BMSCs) after X-ray treatment with low doses only below 0.1 Gy [18,19]
adipose-derived stem cells (ADSCs) of 10 different healthy female donors were obtained from human reduction mammoplasties and pooled to avoid donor-specific effects, as well as to enhance the experimental reproducibility

Summary

Introduction

In Germany, low-dose radiation therapy (LD-RT) is an approved and commonly used option in the treatment of degenerative bone and inflammatory diseases [1], such as heel spur and osteoarthritis [2,3,4]. The success of this therapy is due to the anti-inflammatory and immune modulatory response in humans to LD-RT [5,6,7] mediated by the inhibition of the inflammatory cascade. In the following this particular dose range below 0.1 Gy is referred to as low-dose (LD)

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