The thesis is devoted to the decision of an important scientific and practical task – the study of morphological, immunophenotypic, functional characteristics of mesenchymal stem cells of different origin and evaluation of their systemic influence on the tumor process in recipient animals.
New technologies for obtaining stem cells from the adipose tissue of the dog, horse, mouse, and from a cat's nervous tissue were proposed, and the technology for obtaining stem cells from the mouse red bone marrow was optimized.
New scientific data concerning morphology, functional state of mesenchimal stem cells from red bone marrow and the adipose tissue of the different origin on the early and late passages were obtained.
It was found that the stem cells of red bone marrow culture compared to adipose and nervous tissue have differences in the polyunsaturated fatty acids content. At the same time stem cells from red bone marrow culture, adipose and nervous tissue had common features of the fatty acid spectrum, which are characteristic for cells with high proliferative potential, resistance to apoptosis; a high ratio of unsaturated linoleic to saturated stearic acid (C18:1/C18.0 = 1.5‒2.18), which reflects the activity of the stearol-CoA desaturase enzyme and the active state of the Wnt/β-catenin signaling pathway, inability to lengthen the chain of saturated fatty acids.
Cell cycle of stem cells and aneuploidy levels from cultures of adipose tissue, red bone marrow on the early and late passages were analyzed. New scientific data on immunophenotype of stem cells from adipose and nervous tissue culture were obtained.
In experiments in vivo it was established that transplantation of stem cells from adipose tissue and bone marrow cultures induced the elevation of the activity of succinate dehydrogenase in hepatocyte’s mitochondria in recipient mice, which suggested of their increased mitotic activity; short-term increase in the relative mass index of the thymus and spleen of recipient animals and the content of lymphoid cells, which gradually recover to normal; increasing the activity of NADP-H2-oxidase of monocytes, macrophages.
According to the results of the studies, it was established that under the systemic influence of allogeneic mesenchymal stem cells in animals with experimentally transmitted Lewis lung cancer, the mass of the primary tumor
and the total volume of metastases increased. Furthermore, there was a faster transition of the tumor process to the vascular stage, which indicated its activation.
The causal relationship between stem cell transplantation and the total volume of metastases with an of influence ɳ 2х=0.74 (p<0.05) was proved.
In recipient animals with transplanted Lewis lung carcinoma under systemic influence of allogenic mesenchymal stem cells it were found disturbance of the mechanisms of programmed cell death of the primary tumor due to reduced apoptosis; an increase in the number of lymphoid cells associated with the tumor, which are involved in the activation of angiogenesis in tumor tissue as producers of vascular endothelial growth factor; alteration of genetic stability of primary tumor cells, characterized by an increase in the number of aneuploids in the primary tumor, as well as an their content among cells of proliferative G2/M+S phases of cell cycle. All of the above indicates more malignant phenotype of primary tumor cells.
