The rat spermatogenesis after injection of paclitaxel (antitumor agent).

Morphological and functional characteristics of spermatogenesis in rats were studied during the early and delayed periods after single injection of paclitaxel (antitumor agent) in the maximum tolerated dose. The drug induced structural changes in the gonads associated with oligospermia and increased number of pathological forms of spermatozoa with reduced functional activity.

Potentiation of the stimulatory effect of erythropoietin on erythropoiesis by antiserotonin drug during cytostatic myelosuppression.

Combined stimulatory effect of antiserotonin drug and erythropoietin on the bone marrow erythropoiesis was studied under conditions of cytostatic myelosuppression. The stimulatory effect of erythropoietin on regeneration of the hemopoietic erythroid stem increased, if serotonin mediation in the CNS was disordered before induction of cytostatic myelosuppression. The stimulatory effect of a combination of cyproheptadine and epocrine (experimental group) significantly surpassed that of cyproheptadine and epocrine monotherapies. The increase in the content of erythroid elements in the blood system of experimental animals was due to recovery of the structural and functional integrity of the hemopoietic tissue (at the expense of reduction of the suppressive effect of CNS serotonin on the formation of erythroid hemopoietic islets) and simultaneous stimulation of division and maturation of erythroid precursors with epocrine.

Role of mesenchymal precursor cells in the stimulation of wound healing under the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor.

On the model of skin flap we studied the possibility of stimulating the processes of wound healing with a preparation containing ultralow doses of antibodies to granulocytic colony-stimulating factor. The preparation accelerated tissue regeneration against the background of mobilization of bone marrow mesenchymal precursor cells into circulation accompanied by an increase in the number of stromal precursor cells in the area of lesion.

Role of central adrenergic structures in the regulation of granulocytopoiesis during cytostatic treatment.

We studied the role of central adrenergic structures in the regulation of granulocytic hemopoietic stem during cytostatic treatment. It was found that brain norepinephrine promoted the decrease in functional activity of adherent mononuclears of the hemopoiesis-inducing environment, cytokine-dependent and alpha-adrenergic mechanisms of regulation of division and maturation of granulomonocytic precursors under conditions of cyclophosphamide treatment. Under conditions of 5-fluorouracil treatment, the effect of the adrenergic system was aimed at the formation of granulocytic and fibroblast-type cell complexes, activation of the production of colony-forming activity by microenvironmental cells, and acceleration of maturation of neutrophilic granulocytes associated with the system of granulocytic CSF and peripheral alpha-adrenergic structures.

Immune reactions in the progeny of female rats treated with paclitaxel.

Immune reactions of the progeny of female Wistar rats injected with paclitaxel a single MPD of 1 and 3 months before mating with intact males were studied. Thymic hyperplasia was detected in the progeny of female rats mated 1 month after treatment. Disorders in the antibody-specific and antibody-nonspecific mechanisms of the immune response were detected in the progeny of females mated with intact males 3 months after cytostatic treatment.

Role of Thy-1,2+ cells in the regulation of hemopoiesis during severe hypoxia.

We studied the state of the bone marrow Thy-1,2+ cell pool under conditions of severe hypoxia. T cell mechanisms of hemopoiesis regulation are preserved under conditions of severe oxygen deficiency due to changes in functional properties of Thy-1,2+ cells. We revealed an indirect (mediated through cooperation with adherent myelokaryocytes) stimulating effect of Thy-1,2+ cells on erythroid precursors as well as direct and indirect feeder effects of these cells on granulocyte-monocyte precursors.

Dopaminergic regulation of granulocytopoiesis during cytostatic-induced myelosuppressions.

The role of the dopaminergic system in the regulation of the granulocytic hemopoietic stem was studied after administration of cyclophosphamide and 5-fluorouracil. Dopamine in the central nervous system promotes the development of cytostatic-induced myelosuppressions. The inhibitory effect of dopaminergic structures on granulocytopoiesis after administration the fluoropyrimidine antimetabolite was of shorter duration compared to that observed in experiments with the alkylating agent. The inhibitory effect of brain dopamine is associated with a decrease in proliferative activity and differentiation of granulomonocytic precursors, prevention of hemopoietic islet formation, and impairment of secretion of colony-stimulating activity in adherent cells of the hemopoiesis-inducing microenvironment. Cyclophosphamide and 5-fluorouracil had different effects on the rate of hemopoietic tissue regeneration, which was related to specific interaction between distant regulatory structures and hemopoiesis-inducing microenvironment and differences in the influence of cytostatics on hemopoietic and stromal cells.

Mechanism of mobilization of mesenchymal stem cell under the effect of granulocyte colony-stimulating factor.

We studied the role of cell components and extracellular matrix of the microenvironment in the mechanisms of mobilization of mesenchymal bone marrow stem cells under the effect of granulocyte colony-stimulating factor in vitro and in vivo on CBA/CaLac mice. It was found that the mechanisms underlying the dissociation effect of granulocyte colony-stimulating factor do not include its direct effect on the interaction of precursor cells with fibronectin. The major role in this process is played by changes in functional state of stromal precursors and cell component of the microenvironment induced by granulocytic colony-stimulating factor and mediated by regulatory systems of the microorganism.

Mechanisms of mobilization of mesenchymal precursor cell under the effect of granulocytic colony-stimulating factor and hyaluronidase.

Binding of mesenchymal precursor cells to intact extracellular matrix and stroma increased under the effect of hyaluronidase and decreased after treatment of adhesion substrates with the enzyme. The stimulation of the release of progenitor elements into the blood by granulocytic CSF depended on the interaction of mesenchymal precursors with the feeder stimulating bone marrow microenvironment. Additional in vivo treatment with hyaluronidase potentiated mobilization of precursor cells by granulocytic CSF against the background of increased affinity of precursor to the stroma.

Effect of dimethylsulfoxide on the functions of mesenchymal and hemopoietic precursors.

The effects of dimethylsulfoxide on the state of mesenchymal precursors in vivo were demonstrated. Treatment with dimethylsulfoxide reduced the content of stromal clonogenic elements in the bone marrow and inhibited mobilization of mesenchymal precursors induced by granulocyte colony-stimulating factor. In in vitro system, dimethylsulfoxide inhibited proliferation of fibroblast, erythroid, and granulomonocytic colony-forming units and stimulates maturation of hemopoietic precursors.

Role of hyaluronidase in the regulation of functions of mesenchymal precursor cells.

The possibility of using hyaluronidase for the regulation of the state of different pools of mesenchymal precursors in vivo was demonstrated. The reaction of mesenchymal precursor cells depended on the dose of the enzyme. Administration of hyaluronidase in a dose of 20 U/mouse increased the content of stromal precursors and mesenchymal stem cells in the bone marrow and promotes mobilization of precursor cells induced by granulocyte CSF. Administration of high dose of hyaluronidase (100 U/mouse) reduced the content of mesenchymal precursors in hemopoietic tissue and abolished granulocyte CSF-induced mobilization of mesenchymal precursor cells of different maturity.

State of stem cell pools in experimental diabetes mellitus.

We studied the state of pools of mesenchymal precursor cells of different maturity in the bone marrow and peripheral blood and the dynamics of the content of regional parenchymal stem cells and stromal precursors in the pancreas during experimental diabetes mellitus. Reduced content of organ-specific stem cells and increased content of stromal precursors in the pancreas in the absence of compensatory reaction of deep reserve mechanisms, mesenchymal bone marrow cells, were revealed.

Participation of mesenchymal precursor cells in wound healing on skin flap model.

We studied the state of different pools of mesenchymal precursor cells in the bone marrow, peripheral blood, and wound surface after modeling of tissue damage by skin flap removal. The participation of regional and circulating stromal precursors in the healing of skin defect and the absence of compensatory reaction of the regeneratory process deep reserve, mesenchymal stem cells of the bone marrow, was demonstrated.

Effect of cytostatics on bone marrow stem cells.

Morphological composition of the bone marrow, content of hemopoietic precursors, intensity of their proliferation and differentiation, and the size of mesenchymal precursor pool were studied in experiments on CBA/CaLac mice with myelosuppression induced by adriamycin, cyclophosphamide, or 5-fluorouracil in the maximum tolerated doses. The dynamics of changes in the content of granulomonocyte precursors in the bone marrow after cytostatic treatment was similar to that of erythroid precursors. Changes in the content of stromal mechanocytes were specific for each cytostatic. Different character of the reaction of the hemopoietic and mesenchymal stem cells to the test cytostatics was demonstrated.

Effect of granulocyte colony-stimulating factor on kinetics of hemopoietic precursors in regenerating bone marrow.

We studied processes of proliferation and differentiation of hemopoietic precursor cells in mice treated with granulocyte CSF under conditions of cytostatic myelodepression. It was found that the hemostimulating effect of original granulocyte CSF preparation consists in accelerated maturation of hemopoietic precursors and increased content of DNA-synthesizing CFU-GM in the bone marrow.

Morphological and functional state of rat ovaries in early and late periods after administration of platinum cytostatics.

Experiments on Wistar rats showed that cisplatin and carboplatin induced similar morphological alterations in the ovaries. Both agents reduced the number of structural and functional elements, but the effect of cisplatin was more pronounced. Morphological changes observed in the early period after injection of the preparations were accompanied by prolongation of the estrous cycle, which was longer in rats treated with carboplatin. Partial and reversible sterility was observed in females at the early terms after cisplatin treatment.

Cytogenetic effects of antibodies to gamma-interferon in ultralow doses.

Single and course administration of ultralow doses of antibodies gamma-interferon did not increase the incidence of cytogenetic abnormalities in bone marrow cells from BALB/c mice and produced no genotoxic effect on Drosophila melanogaster wing cells in the test of somatic mosaicism.

Mutagenic activity of potentiated antibodies to erythropoietin.

Single and repeated administration of ultralow doses of antibodies to erythropoietin did not increase the count of aberrant metaphases in bone marrow cells of BALB/c mice and were not genotoxic for Drosophila melanogaster wing cells in the test of somatic mosaicism.

Role of glucocorticoids in the regulation of bone marrow hemopoiesis in stress reaction.

We have studied the role played by glucocorticoids in the regulation of bone marrow hemopoiesis in stress reaction. The effector influence of the adrenal cortex hormones on the committed precursor cells of erythro-granulo-monocytopoiesis mediated through the T-cell system has been confirmed. Glucocorticosteroids initiate homing of the T-cell regulators of myelopoiesis of the Lyt-1+ phenotype from the lymphoid organs into the bone marrow.