Radiation Sensitivity of Adipose-Derived Stem Cells Isolated from Breast Tissue

Abstract

Within their niche, adipose-derived stem cells (ADSCs) are essential for homeostasis as well as for regeneration. Therefore, the interest of physicians is to use ADSCs as a tool for radiation oncology and regenerative medicine. To investigate related risks, this study analyses the radiation response of adult stem cells isolated from the adipose tissue of the female breast. To avoid donor-specific effects, ADSCs isolated from breast reduction mammoplasties of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival fraction assay was used to classify the radiation sensitivity in comparison to a more radiation-sensitive (ZR-75-1), moderately sensitive (MCF-7), and resistant (MCF10A) cell lines. Afterwards, cytotoxicity and genotoxicity of irradiation on ADSCs were investigated. On the basis of clonogenic cell survival rates of ADSCs after irradiation, we assign ADSCs an intermediate radiation sensitivity. Furthermore, a high repair capacity of double-strand breaks is related to an altered cell cycle arrest and increased expression of cyclin-dependent kinase (CDK) inhibitor p21. ADSCs isolated from breast tissue exhibit intermediate radiation sensitivity, caused by functional repair mechanisms. Therefore, we propose ADSCs to be a promising tool in radiation oncology.

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

“…Furthermore, exposure to medium IR resulted in a strong reduction of the surviving fraction of 60% (1.0 Gy) and 80% (2.0 Gy). These results are comparable to further studies analysing the effect of IR on ADSCs, which however, used only 0.5 Gy as the smallest dose [33,37]. In contrast to IR in the high dose range with a clear dose-response relationship, after irradiation in the low and medium dose range non-linear dose-response relationships are already known from a lot of studies [38].…”

“…For this study, 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. In our previous work we have already demonstrated that the endpoints of radiobiological investigations in pooled ADSCs (pADSCs; N = 10) are comparable to the average of the single analysis of each donor [33]. Due to slight differences in the growth rate of ADSCs of different donors, a relatively high number of 10 donors were chosen for pooling and experiments were performed only a few doubling times after cell pooling as described before [33].…”

“…In our previous work we have already demonstrated that the endpoints of radiobiological investigations in pooled ADSCs (pADSCs; N = 10) are comparable to the average of the single analysis of each donor [33]. Due to slight differences in the growth rate of ADSCs of different donors, a relatively high number of 10 donors were chosen for pooling and experiments were performed only a few doubling times after cell pooling as described before [33]. Moreover, the isolated cells were characterized by the minimal criteria for the declaration of multipotent mesenchymal stromal cells [33,34], defined by the position statement of The International Society for Cellular Therapy in 2006 [33,34,35].…”

“…Several research groups have already demonstrated that medium (>2 Gy) and moderate radiation doses (0.5 Gy) induce negative side-effects in ADSCs regarding the cell proliferation and survival fraction [33,36,37], but to date the impact of low radiation doses (≤0.1 Gy) remain unclear. For this reason, we first examined the side-effects in ADSCs after LD-IR.…”

“…This time-dependency was only significant for the radiation dose of 0.096 Gy (ANOVA: p < 0.05). The growth kinetic of ADSCs is characterized by a relatively high population doubling time of about 60 to 90 h [33,43], depending on various donor factors such as age, body mass index (BMI), and others reviewed in [44]. Accordingly, the cell cycle was not completely traversed within these time periods of 24 and 48 h. Likewise, it can be assumed that the cell seeding procedure 24 h before IR has synchronized the pADSCs in the cell cycle to a certain extent.…”