Characteristics of tumors that have developed in mice injected with syngenic irradiated mesenchymal stem cells of bone marrow

Abstract

Mesenchymal stem cells (MSCs) are found in virtually all organs and tissues. These cells can presumably be transformed into tumor stem cells by genotoxic factors and, subsequently, initiate tumor growth. The aim of the present work consisted in analysis of the possibility of malignant transformation of cultured MSCs from the bone marrow (BM) of mice after in vitro exposure to γ-radiation and in the characterization of biochemical and histological features of tumors that developed after the transplantation of BM MSCs to syngenic mice. Two of five mice developed tumors 3 to 4 months after the subcutaneous injection of BM MSCs irradiated at a dose of 1 Gy, five of five animals developed tumors after the administration of BM MSCs irradiated at a dose of 6 Gy, and only one of five mice injected with nonirradiated BM MSCs developed a tumor 6 months after cell transplantation. Telomerase activity in a tumor that developed from BM MSCs irradiated at a dose of 6 Gy was twice as high as that in the tumor that developed from BM MSCs irradiated at a dose of 1 Gy. The histological structure of the neoplasms corresponded to that of multicomponent mesenchymoma, a malignant tumor also termed “a mix of sarcomas.” The tumors consisted of tissue fragments of different histological types. Thus, BM MSCs exposed to 1 or 6 Gy of radiation can be transformed into tumor cells and give rise to multicomponent mesenchymomas, whereas malignant transformation of control BM MSCs occurs much less often.