Cancer stem cells (CSCs) are highly resistant to chemo- and radiotherapy. The aim of this work was to study the effect of metformin on the radiosensitivity of MCF-7 cells cultivated as mammospheres enriched with CSCs. One hour after the addition of metformin at a nontoxic concentration of 0.25 mmol/L, cells of mammospheres were exposed to γ-radiation at a dose of 2 Gy or reactor γ,n-radiation at a dose of 1 Gy. After 24 hours of cultivation, the drug was removed. Six days after irradiation, the total number of cells was calculated by a hemocytometer, then the percentage of CSCs with the CD44+/CD24–/low phenotype was determined, and the number of CSCs in the samples was calculated. The exposure to γ,n-radiation led to a significant decrease in both the total number of cells and CSCs compared with γ-radiation. The combined exposure to metformin and γ- or γ,n-radiation led to a significant decrease in both the total number of cells and CSCs compared with the exposure to γ-or γ,n-radiation only (p < 0.05). Thus, γ,n-radiation is more effective with respect to eliminating the MCF-7 CSCs than γ-radiation. Metformin increases the sensitivity of the MCF-7 CSCs to γ-and γ,n-radiation.

Mesenchymal stem cells from the adipose tissue (AT MSC) and the bone marrow (BM MSC) stimulated migration of melanoma B16 cells, while mammary adenocarcinoma Ca755 cells stimulated migration of mesenchymal stem cells. Mesenchymal stem cells retained these properties at late terms after γ-irradiation in vitro . Tumors that developed after injection of Ca755 cells alone and in combinations with BM MSC or AT MSC had similar histological structure corresponding to breast adenocarcinoma. Only AT MSC stimulated tumor growth, which was determined by more intensive secretion of factors stimulating proliferation of tumor cells, including chemokine CCL2. The use of AT MSC in regenerative medicine requires careful monitoring of the absence of tumors in patients.

We studied the effect of mesenchymal stem cells from the bone marrow and adipose tissue on the growth rate of melanoma B16 and mammary adenocarcinoma Ca755 tumors after their co-administration with tumor cells to syngeneic mice. Stimulation of tumor growth and formation of melanoma metastases in the lungs was found under the influence of adipose tissue-derived, but not bone marrow-derived stem cells. At delayed terms after irradiation in sublethal doses, the adipose tissue-derived mesenchymal stem cells also stimulated the tumor growth. Stimulation of the tumor growth by adipose tissue-derived mesenchymal stem cells was caused by factors secreted by these cells. Transplantation of mesenchymal stem cells to humans is possible only after accurate exclusion of malignant tumors.