ABSTRACT
We studied the effect of hyaluronate-endo-ß-N-acetylhexosaminidase on the secretory function of the liver and bone marrow microenvironment cells in chronic hepatitis. Enhanced production of substances stimulating parenchymal tissue-specific precursors and stem cell homing factors by liver cells was revealed. At the same time, production of SDF-1 and other chemoattractants and adhesion factors of progenitor cells by bone marrow elements was reduced.
Subject(s)
Bone Marrow Cells/metabolism , Chemokine CXCL12/biosynthesis , Hepatitis, Chronic/metabolism , Liver/metabolism , Polyethylene Glycols/pharmacology , Stem Cells/drug effects , beta-N-Acetylhexosaminidases/pharmacology , Animals , Bone Marrow Cells/drug effects , Cell Movement/drug effects , Cellular Microenvironment/drug effects , Hyaluronoglucosaminidase , Liver/cytology , Liver/drug effects , Male , Mice , Mice, Inbred C57BL , Stem Cells/metabolismABSTRACT
A mixture of diterpene alkaloids of Aconitum baicalense exhibited pronounced regenerative hemostimulating properties on the model of cytostatic myelosuppression. The therapeutic effect is based on activation of hemopoietic progenitor cells against the background of increased feeder capacity of stromal compartment of the hemopoiesis-inducing microenvironment and decreased count of mesenchymal stem cells in the bone marrow.
Subject(s)
Aconitum/chemistry , Alkaloids/pharmacology , Diterpenes/pharmacology , Hematopoiesis/drug effects , Hematopoietic Stem Cells/drug effects , Regenerative Medicine/methods , Alkaloids/analysis , Animals , Bone Marrow Cells/drug effects , Cellular Microenvironment , Diterpenes/analysis , Fluorouracil , MiceABSTRACT
Pronounced regenerative effects of alkaloid napelline extracted from Aconitum baicalense on granulocytic hemopoiesis were revealed in the model of cytostatic myelosuppression. Activation of functions of hemopoietic progenitor cells along with increased feeder capacity of the stromal elements in the hemopoiesis inducing microenvironment with decreased levels mesenchymal progenitor cells in the bone marrow are the mechanisms underlying the hemostimulating action of this substance.
Subject(s)
Hematopoiesis/drug effects , Aconitine/pharmacology , Animals , Bone Marrow/drug effects , Bone Marrow Cells/drug effects , Bone Marrow Cells/physiology , Cells, Cultured , Cytostatic Agents/pharmacology , Fluorouracil/pharmacology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice, Inbred CBA , Myeloid Progenitor Cells/drug effects , Myeloid Progenitor Cells/physiology , Regenerative MedicineABSTRACT
We studied the secretory function of the liver and bone marrow microenvironment cells under conditions of chronic CCl4-induced hepatitis. Enhanced production of substances stimulating parenchymal tissue-specific precursors and stem cell homing factors by liver cells was observed. In situ binding of stem cells by bone marrow elements increased due to production of various cooperation and adhesion factors against the background of reduced SDF-1 secretion.
Subject(s)
Bone Marrow Cells/metabolism , Chemical and Drug Induced Liver Injury, Chronic/pathology , Hepatitis, Chronic/pathology , Liver/cytology , Liver/metabolism , Stem Cells/physiology , Animals , Carbon Tetrachloride , Cell Movement , Cellular Microenvironment , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Chemokine CXCL12/metabolism , Culture Media, Conditioned/chemistry , Hepatitis, Chronic/metabolism , Male , Mice , Mice, Inbred C57BL , Stem Cell NicheABSTRACT
High hepatoprotective activity of granulocytic CSF and hyaluronidase immobilized using electron-beam immobilization technology was demonstrated on the model of CCl(4)-induced hepatitis: the preparations produced anticholestatic, anti-inflammatory, and antisclerotic effects. These effects developed against the background of stimulation of bone marrow multipotent precursor cells and their mobilization into circulation accompanied by an increase in the content of parenchymatous progenitor cells in the liver. The most pronounced positive effect was observed in combined treatment with the test preparations.
Subject(s)
Enzymes, Immobilized/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hepatitis, Chronic/drug therapy , Hyaluronoglucosaminidase/therapeutic use , Animals , Male , Mice , Nanotechnology , Rats , Rats, Wistar , Regenerative MedicineABSTRACT
Pharmacological characteristics of somatotropin pegylated using electron-beam synthesis nanotechnology (PEG-STH) were studied. Oral PEG-STH stimulated the intensity of protein and lipid metabolism and endochondral bone growth without modifying the processes of periosteal and endosteal bone formation. Specific activity of this substance administered orally significantly surpassed that of parenteral non-modified growth hormone.
Subject(s)
Bone Development/drug effects , Human Growth Hormone/pharmacology , Lipid Metabolism/drug effects , Nanotechnology , Polyethylene Glycols , Proteins/metabolism , Animals , Male , Rats , Rats, WistarABSTRACT
The effect of Dicarbamin preparation on hemopoiesis suppressed with cyclophosphamide was studied in animal experiments. It was shown that Dicarbamin produced a protective effect on granulocytic hemopoietic steam. This property of the preparation is determined by both protection of immature granulocytic cells at early terms after cytostatic treatment and more active maturation of neutrophils in the bone marrow due to enhanced secretion of humoral factors by elements of hemopoietic environment at late terms of the experiment.
Subject(s)
Cytostatic Agents/pharmacology , Granulocytes/drug effects , Hematopoiesis/drug effects , Imidazoles/pharmacology , Protective Agents/pharmacology , Animals , Caproates , Cyclophosphamide/pharmacology , Male , Mice , Mice, Inbred CBA , Statistics, NonparametricABSTRACT
Granulocytic CSF pegylated using electron-beam synthesis nanotechnology exhibits pronounced granulomonocytopoiesis-stimulating and SC-mobilizing activity. More potent stimulation of committed precursors against the background of less pronounced activation of polypotent hemopoietic cells is a peculiarity of hemostimulating action of pegylated using electron-beam synthesis nanotechnology granulocytic CSF in comparison with its non-modified analog. The mobilizing effect of pegylated using electron-beam synthesis nanotechnology granulocytic CSF on early progenitor elements surpasses that of non-conjugated cytokine.
Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Hematinics/pharmacology , Polyethylene Glycols/pharmacology , Animals , Bone Marrow/drug effects , Bone Marrow Cells/drug effects , Cell Count , Cyclophosphamide/pharmacology , Granulocyte Colony-Stimulating Factor/chemical synthesis , Granulocytes/cytology , Granulocytes/drug effects , Hematinics/chemical synthesis , Hematopoiesis/drug effects , Humans , Immunosuppressive Agents/pharmacology , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/physiology , Mice , Mice, Inbred CBA , Nanotechnology , Neutrophils/cytology , Neutrophils/drug effects , Poisson Distribution , Polyethylene Glycols/chemical synthesis , Statistics, NonparametricABSTRACT
Immobilized hyaluronidase (nanotechnology method of electron-beam synthesis) exhibited high hepatoprotective activity on the model of Cl4-induced hepatitis. This agent produced anticholestatic, anti-inflammatory, and antisclerotic effects. These effects were shown to accompany stimulation of multipotent bone marrow precursors, mobilization of these cells into the peripheral blood, and cell migration to the target organ increasing the number of parenchymal progenitor cells in the liver. The mechanisms for targeted migration of progenitor cells suggest a decrease in SDF-1 production by bone marrow stromal cells and increase in the synthesis of this factor by microenvironmental cells of the liver tissue.
Subject(s)
Cytoprotection , Enzymes, Immobilized/therapeutic use , Hepatitis, Animal/drug therapy , Hyaluronoglucosaminidase/therapeutic use , Liver/drug effects , Multipotent Stem Cells/drug effects , Animals , Biomarkers/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Carbon Tetrachloride , Cell Movement/drug effects , Cellular Microenvironment/drug effects , Chemokine CXCL12/metabolism , Enzymes, Immobilized/administration & dosage , Enzymes, Immobilized/chemistry , Hepatitis, Animal/metabolism , Hepatitis, Animal/pathology , Hyaluronoglucosaminidase/administration & dosage , Hyaluronoglucosaminidase/chemistry , Liver/metabolism , Liver/pathology , Mice , Multipotent Stem Cells/cytology , Nanotechnology , Rats , Stromal Cells/cytology , Stromal Cells/drug effectsABSTRACT
In vitro experiments demonstrated increased colony-forming capacity of erythroid, granulomonocytic, and mesenchymal progenitors of the bone marrow and parenchymal progenitor elements of the liver after treatment with immobilized hyaluronidase. Increased sensitivity of these progenitor cells to erythropoietin, granulocyte colony-stimulating factor, fibroblast growth factor, and stem cell factor, respectively, was demonstrated. Immobilized hyaluronidase enhanced the formation of tissue-specific hepatic CFU against the background of reduced yield of stromal precursors in liver tissue culture containing insulin.
Subject(s)
Enzymes, Immobilized/pharmacology , Hematopoietic Stem Cells/drug effects , Hyaluronoglucosaminidase/pharmacology , Mesenchymal Stem Cells/drug effects , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Colony-Forming Units Assay , Enzymes, Immobilized/chemistry , Erythropoietin/pharmacology , Fibroblast Growth Factors/pharmacology , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cells/cytology , Hyaluronoglucosaminidase/chemistry , Insulin/metabolism , Insulin/pharmacology , Liver/cytology , Liver/drug effects , Male , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred CBA , Nanotechnology , Stem Cell Factor/pharmacology , Tissue Culture TechniquesABSTRACT
The hemostimulating effect of erythropoietin immobilized by the nanotechnology method of electron-beam synthesis was studied on the model of carboplatin-induced myelosuppression. Subcutaneous injection or oral administration of immobilized erythropoietin was followed by stimulation of erythropoiesis. The effect was most pronounced after parenteral treatment with this agent. The increase in proliferative activity and maturation of erythroid precursor cells serve as a factor determining acceleration of reparative processes in the hemopoietic tissue.
Subject(s)
Drug Carriers/chemistry , Erythropoietin/pharmacology , Immobilized Proteins/pharmacology , Polyethylene Glycols/chemistry , Anemia/blood , Anemia/chemically induced , Anemia/drug therapy , Animals , Bone Marrow/drug effects , Bone Marrow/pathology , Carboplatin , Cell Count , Cells, Cultured , Erythropoietin/chemistry , Erythropoietin/pharmacokinetics , Erythropoietin/therapeutic use , Hematopoiesis/drug effects , Immobilized Proteins/chemistry , Immobilized Proteins/therapeutic use , Mice , Mice, Inbred CBA , Nanotechnology , Reticulocytes/drug effects , Reticulocytes/pathologyABSTRACT
We studied the effect of immobilized hyaluronidase on hemopoiesis under conditions of cyclophosphamide-induced suppression. The preparation was shown to possess high hemostimulating activity. The stimulatory effect of hyaluronidase on the erithron was more pronounced than its effect on the granulocytic hemopoietic stem due to increase in functional activity of hemopoietic precursors and hemopoiesis-inducing microenvironment.
