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.

Mechanisms underlying the effects of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of damaged pancreatic tissue in experimental diabetes mellitus.

Using the model of alloxan-induced diabetes mellitus on rats we demonstrated the effect of ultralow doses of antibodies to granulocytic colony-stimulating factor on recovery of the pancreas and normalization of blood glucose concentration. The preparation produced an antiinflammatory and antisclerotic effects associated with activation of stem cells and their determined homing into the pancreas.

A comparative study of stimulation of erythropoiesis during renal anemia with the preparation of antibodies against erythropoietin in ultralow doses and Recormon.

We compared the stimulatory effects of a preparation of antibodies against erythropoietin in ultralow doses (Poetam) and recombinant erythropoietin (Recormon) on erythropoiesis that was suppressed by carboplatin. Both drugs possessed high erythropoiesis-stimulating activity, which was manifested in an increase in the number of erythrokaryocytes and erythroid precursors in hemopoietic tissue and count of erythrokaryocytes and reticulocytes in the peripheral blood during postcytostatic recovery. Recormon produced a rapid and short-term stimulatory effect on the erythron.

Mechanisms of regulation of hemopoiesis during experimental cytostatic myelosuppression induced by carboplatin.

The mechanisms of suppression and recovery of the bone marrow erythroid stem were studied on the model of myelosuppression induced by administration of carboplatin in the maximum tolerated dose. Single administration of the cytostatic led to the development of long-term hypoplasia of hemopoiesis. Despite enhanced proliferation of erythroid precursor caused by increased erythropoietic activity of blood plasma and bone marrow cells, inhibition of cell maturation prevented recovery of the content of morphologically recognizable erythrokaryocytes in the bone marrow.

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.

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.

Specific activities of poetam preparation (superlow-doses of antibodies to erythropoietin) and recombinant erythropoietin.

We compared the capacity of superlow-dose of antibodies to erythropoietin (Poetam) and recombinant erythropoietin (Recormon) to stimulate the recovery of adriamycin-suppressed erythropoiesis in mice. Both preparations exhibited high erythron activation capacity and considerably increased the content of erythrocytes and reticulocytes in the peripheral blood and content of erythrokaryocytes and erythroid precursors in the hemopoietic tissue of experimental animals. The effect of Recormon manifested immediately after injection, while the effect of Poetam was somewhat delayed, but more lasting (due to activation of host erythropoietin system).

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.

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.

Function of hemopoietic stem cells under conditions of cytostatic myelosuppression and treatment with hemostimilators.

We compared the function of hemopoietic stem cells under conditions of cytostatic myelosuppression (cyclophosphamide treatment) and during treatment with granulocytopoiesis stimulators. It was found that unipotent hemopoietic precursor cells are most sensitive to cyclophosphamide. Different effects of hemostimulators on stem cells are determined by different proportions between proliferation and differentiation processes.

Pharmacological regulation of functional activity of stem cells in restoration of the myocardium during the postinfarction period.

The effect of granulocytic CSF on myocardial tissue recovery after acute myocardial infarction was studied on rats. A course of granulocytic CSF after ligation of the left coronary artery normalized ECG parameters and morphological picture of the myocardium 1 month after treatment. It was shown on mouse model of myocardial infarction that this process was associated with more intensive mobilization and homing of mesenchymal stem cells in the heart.

Erythropoietic activity of preparations containing receptors and antibodies to erythropoietin in ultralow doses.

We compared the erythropoiesis-stimulating effects of ultralow doses of erythropoietin receptors and antibodies to erythropoietin in intact mice. Antibodies to erythropoietin, but not erythropoietin receptors, possessed considerable erythropoiesis-activating properties.

Role of humoral factors in the regulation of hemopoiesis during cytostatic-induced myelosuppression.

The content of hemopoietic precursors in the bone marrow, its morphological composition, production of hemopoietic growth factors by cells of the hemopoietic microenvironment, erythropoietic activity, and plasma content of endogenous erythropoietin were studied in CBA/CaLac mice with hypoplasia of hemopoiesis induced by adriamycin in a maximum permissible dose. Cytostatic treatment affected production of substances determining erythropoietic activity by adherent and nonadherent cells of the bone marrow. Erythropoietic activity of peripheral blood plasma considerably increased.

Reactions of hemopoietic granulocytic stem in hypoxia of different severity.

We studied the reactions of granulocytic hemopoietic stem after acute hypoxia and during the development of posthypoxic encephalopathy. Damage to brain structures was associated with intensification of the bone marrow hemopoiesis due to activation of hemopoiesis-inducing microenvironment and more intense formation of hemopoietic islets, despite reduced proliferative capacity of granulocytic precursors.

Mechanisms of changes in the erythroid hemopoietic stem during hypoxias of different severity.

Brain pathology (acute hypoxia and posthypoxic encephalopathy) is associated with less pronounced hyperplasia of the bone marrow erythroid stem (due to decreased count of proliferating committed precursors) and hemolytic anemia, while secretory activity of stromal cells of the hemopoiesis-inducing microenvironment is not impaired. Severe oxygen deficiency affects erythroid precursors and impairs production of functionally normal erythrocytes in the posthypoxic period.

Role of cell-cell interactions in the regulation of hemopoiesis during cytostatic-induced myelosuppression.

The content of hemopoietic precursors in the bone marrow, its morphological composition, structural and functional organization, binding of hemopoietic precursors by adherent cells, and expression of receptors for erythroblasts and sialoadhesin on bone marrow macrophages were studied in CBA/CaLac mice with hypoplasia of hemopoiesis caused by etoposide in a maximum permissible dose. It was found that recovery of hemopoiesis after cytostatic treatment was related to accelerated maturation of hemopoietic precursors and increased ability of microenvironmental cells to bind hemopoietic cells.

Role of hemopoietic growth factors in regeneration of hemopoiesis during etoposide-induced myelosuppression.

We studied structural and functional organization of the bone marrow, production of hemopoietic growth factors by hemopoietic cells, and plasma colony-stimulating and erythropoietic activities in CBA/CaLac mice treated with etoposide. The effects of etoposide on cultured hemopoietic and microenvironmental cells were also evaluated. Our results indicate that hemopoietic growth factors secreted by adherent bone marrow cells play the major role in the normalization of hemopoiesis during etoposide-induced myelosuppression.

Mechanisms of myelopoiesis stimulation with pantohematogen and granulocyte colony-stimulating factor during cytostatic myelosuppression.

We compared hemopoiesis-stimulating activities of dry pantohematogen and recombinant granulocyte colony-stimulating factor under conditions of cyclophosphamide-induced myelosuppression. These preparations stimulated regeneration of bone marrow granulomonocytopoiesis by various mechanisms.

Involvement of bone marrow fibroblasts in the recovery of granulocytopoiesis after cytostatic-induced myelosuppression.

The effects of anticancer drugs whose action is mediated by different mechanisms on activity of bone marrow fibroblasts and their role in the regulation of granulocytopoiesis recovery after cytostatic treatment were studied. The antimetabolite 5-fluorouracil strongly suppressed, while the anthracycline antibiotic adriamycin and the alkylating agent cyclophosphamide stimulated function of stromal cells. This largely accounted for different dynamics of recovery of the bone marrow neutrophil lineage.