A MORPHOFUNCTIONAL STUDY OF MESENCHYMAL STEM CELLS’ EFFECTS ON SARCOMA М-1

DOI: https://doi.org/None

V.V. Yuzhakov (1), L.E. Sevan'kaeva (1), A.G. Konoplyannikov (1), L.N. Bandurko (1), M.A. Konoplyannikov (2), I.E. Ingel (1), N.K. Fomina (1), M.G. Tsyganova (1), S.Sh. Kal'sina (1) 1 -Medical Radiological Research Center, Koroleva street, 4, Obninsk, Russian Federation, 249036; 2 -Federal Research Clinical Center for specialized types of health care and medical technologies of FMBA, Orekhovy boulevard, 28, Moscow, Russian Federation, 115682

Introduction. The one of the most important problems of the modern regenerative medicine is incomplete understanding of the influence of mesenchymal stem cells (MSCs) on the growth of malignant neoplasms. Aim of the study. Analysis of the allogeneic MSCs’ effects on the growth and functional morphology of transplanted connective tissue tumor in rats. Methods. We administered MSCs grown from the bone marrow cell population of Wistar rats into the tail vein of outbred rats from the experimental group, on the 11th day after the sarcoma M-1 implantation. To study the MSCs distribution and localization in the tumor parenchyma, we labeled MSCs in vitro with bromodeoxyuridine (BrdU). The techniques for studying of the tumor reaction on the systemic MSCs transplantation included immunostaining for PCNA, BrdU and CD31, as well as computerized analysis of the microscopic images. We estimated the MSCs’ effects also through the dynamics of the tumor growth and tumor-bearers’ survival in the experimental and control groups. Results. Early after the transplantation, the labeled MSCs localized in the perivascular areas of angiogenesis on the periphery of tumor nodules. A short-term stimulating effect of MSCs on the sarcoma M-1 growth was due to the increase in the proliferative activity of tumor cells mediated by enhanced peritumoral vascularity. However, after the MSCs transplantation, we observed later an opposite trend, with theintensification of the apoptotic death of tumor cells, which finally resulted in the deceleration of the sarcoma M-1 growth and enhancement of the animals’ survival. Conclusion. The single-shot MSCs administration into the rats with sarcoma M-1 had an oncomodulating effect on the growth of malignant neoplasms and increased the tumor-bearers’ survival.
Keywords: 
mesenchymal stem cells, sarcoma М-1, angiogenesis, PCNA, bromodeoxyuridine, CD31
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