Radiosensitising effect of mesenchymal stem cells on sarcoma M-1 under local gamma-irradiation

Abstract

Very little information about effects of mesenchymal stem cells on malignant neoplasms radiosensitivity is available. The research aims to study impact of human mesenchymal stem cells (hMSC) on survival of tumor-bearing animals, tumor growth rate and morphology following single local irradiation of sarcoma M-1 by 60Co γ-rays with dose of 30 Gy. Immunostaining technique forPCNA, CD31, pimonidazole and computer-assisted analysis of microscopic images are used to de-tect the effects. The results demonstrate activation of angiogenesis in tumor growth zones, increase in concentration of proliferating tumor cells in the neoplasm parenchyma, twofold reduction of hy-poxic cells fraction following hMSCs transplantation. Quantitative analysis of impact of transplanted mesenchymal stem cells and local irradiation of the tumor identifies more pronounced radiation in-activation of tumor cells. In post-radiation period the growth rate of irradiated tumor cells reduces by 1.8 times, and cumulative survival fraction of tumor-bearing rats increases by 31%, as compared with the gamma-irradiated stem cells free animals with M-1 sarcoma. The results of research pro-vide opportunity to identify and document radiosensitizing effect of hMSC administered prior to local irradiation of transplantable connective tissue tumor for the first time. There are reasons to suppose that increased radiosensitivity of sarcoma M-1 is caused by reduction of the most radioresistant hy-poxic cells fraction in the irradiated area.