The dissertation is devoted to the study of immunobiological and antitumor properties of the fetal brain neurogenic cells (FBNC) and their humoral factors.
The phenotypic, proliferative, differentiating features of FBNC have been determined in studies in vitro. The dynamics of expression of MHC antigens by FBNC during cultivation and their immunogenicity at introduction into the organism are determined. In studies in vivo, the development and comparative intensity of allospecific cell and humoral immune responses in animal recipients after intraperitoneal and intracerebral introduction of allogenic FBNC has been proved. The expression of MHC antigens by FBNC has been confirmed at a lower level, compared with immunocytes, but sufficient to induce allospecific immune responses. The development of neurospecific immune responses in recipients of allogenic FBNC, in contrast to syngenic, is indicated, certifying the involvement of antibodies to neuroantigens, along with antibodies to alloantigens in immune rejection reactions. The correlation of the intensity and duration of morphological changes in the brain tissue after intracerebral implantation of FBNC with manifestations of allospecific and neurospecific immune responses has been established and their inhibition by immunosuppression with cyclosporin A is confirmed, which substantiates the use of immunosuppression in the neurotransplantation of allogenic FBNC.
The immunomodulatory properties of the conditioned medium (CM) of the rat FBNC were ascertained: the effect on the expression and production of cytokines (TNF-, IL-1β, IL-10, TGF-β2) by peripheral blood mononuclear cells of healthy individuals and patients with brain gliomas in vitro, and stimulation of cytotoxic activity of immunocytes in relation to xenogenic and allogenic tumor cells of glioma at intraperitoneal administration to intact animals. Antitumor properties of the CM in cell cultures of brain gliomas have been established: dose-dependent cytotoxic, antimitotic and antiproliferative effects; increase of expression of markers of apoptosis (CD95, p53) and MHC I, II; reduce of expression of markers of tumor progression (CD133, Ki-67, TGF-1) and immunosuppressive cytokines. Immunomodulatory and antitumor effects of the CM, which reproduce the microscale of the niche of neurogenic stem / progenitor cells in organism, are caused by the presence in its composition of BDNF, TGF-1, IFN-, IL-1β and IL-4. In experimental animals with transplanted cerebral glioma, it has been shown that the CM reduces the ability of glioma cells to induce tumors, increases cytotoxic activity of immunocytes and life expectancy and median survival of animals with tumors after intraperitoneal administration. The antitumor efficacy of allogeneic tumor vaccine, modified by CM, has been proved. The experimental data received in the dissertation study provide the basis for improving the methods of immune therapy of gliomas using biopreparations obtained from FBNC.
