Variability of the biological activity of oxidized titanium implants.

Oxidized titanium is a biologically inert material, but bioinertness reduces biomechanical characteristics of titanium implants. Modification of the structure of oxide surface layer of BT 5-1 titanium by increasing its thickness (by 1.7 times) and pore diameter (by 1.4 times) and by adding phosphorus, aluminum, and zinc oxides to its composition leads to radical modification of its biological characteristics. These implants acquire osteoinductive properties in in vivo systems not found in pure or oxidized BT 1-00 titanium and fairly well maintain in vitro growth of mesenchymal cells.

Evaluation of the efficacy of granulocyte colony-stimulating factor for the treatment of experimental myocardial destruction in mice.

We studied the effects of recombinant granulocytic CSF on heart remodeling in BALB/c mice after cryodestruction. Administration of granulocytic CSF was started 1 day after cryodestruction (subcutaneously, 10 µg/kg/day, for 4 days). As early as after the first injection, leukocytosis in the peripheral blood started to develop, leukocyte count peaked on days 4-6 and returned to normal on day 14. Treatment with granulocytic CSF significantly increased the content of progenitor cells in the bone marrow and led to rapid development of the inflammatory reaction and myocardium infiltration with mononuclear cells. Injections of granulocytic CSF did not reduce scar area, but provided significantly less pronounced heart hypertrophy, which attests to its better functional properties. By day 30 after cryodestruction, control animals and animals receiving granulocytic CSF exhibited similar morphological picture at the site of damage. Thus, our regimen of granulocytic CSF administration produced a mobilizing effect on bone marrow progenitor cells and postinfarction heart remodeling. Direct effects of granulocytic CSF on the heart have to be established for its use in the treatment of myocardial infarction.

Comparative assessment of heart remodeling in rats after experimental coronary stenosis and cryodestruction.

Comparative analysis of myocardial changes due to heart remodeling after experimental coronary stenosis and cryodestruction in rats was performed. Similar picture of heart remodeling was observed in all animals on day 45 irrespective of the type of destruction: hypertrophy of intact myocardium of the left ventricle, formation of extensive connective tissue cicatrix, and similar structural changes in the myocardium adjacent to the damage area. The type of the damaging influence possibly plays a role at the stage of lesion formation. We concluded that the proposed method of cryodestruction induces heart remodeling comparable to that observed after coronary occlusion.

Effect of transplantation of bone marrow cells on morphology of rat myocardium after cryodestruction.

We studied the effects of bone marrow cell transplantation on myocardium of the prenecrotic zone in Wistar rats. Intramyocardial cell transplantation reduced the severity of hypertrophy of myocardium and the degree of its cicatricial degeneration on day 40 after cryodestruction. The morphology of the myocardium in the prenecrotic zone depended on the type of transplanted cells. The course of inflammation was swifter; vascularization of the myocardium was more intensive. The best effect, evaluated by the number of new vessels, was observed after MSC transplantation. Hence, the positive effect of bone marrow cell transplantation is realized at the expense of more rapid structural organization of the damaged site and stimulation of myocardial vascularization.

Transplantation of bone marrow mononuclear cells does not affect postinfarction electrical remodeling of the heart.

We studied the effect of allotransplantation of bone marrow mononuclear cells on postinfarction remodeling of the heart in rats. The cells were transplanted into the periinfarction zone of the heart. The transplantation was performed on day 9 after coronary occlusion. It was found that on day 45 after coronary occlusion myocardial hypertrophy developed, ventricular fibrillation threshold decreased, but myocardial contractility remained within the normal. Allotransplantation of bone marrow mononuclear cells had no effect on myocardial hypertrophy and did not prevent the development of electrical instability of the heart.

Colony-forming cells in rat myocardium after destructive exposure and intramyocardial transplantation of bone marrow cells.

The content of colony-forming cells in myocardial cell culture from the perinecrotic zone of rat heart was evaluated on day 40 after cryodestruction. The mean cellularity after cryodestruction was 12-fold lower than in intact animals. Intramyocardial transplantation of bone marrow cells (mononuclears, mesenchymal stem cells, and mesenchymal stem cells treated with 5-azacitidine) into the perinecrotic zone increased the content of colony-forming cells. After transplantation of mesenchymal stem cells and mesenchymal stem cells treated with 5-azacitidine, the number of colonies reached 33 +/- 7 and 11 +/- 3, the mean cellularity being 2975 +/- 80 and 1105 +/- 42 cells/cm2, respectively. Hence, intramyocardial transplantation of mesenchymal stem cells created an appreciable pool of colony-forming cells in the myocardial perinecrotic zone. Treatment with 5-azacitidine reduced survival of mesenchymal stem cells after intramyocardial transplantation.

Inotropic response of the myocardium in rats with postinfarction cardiosclerosis exposed to extrasystolic treatment.

The inotropic response of the myocardium to extrasystolic treatment was studied on isolated perfused papillary muscles from rats with postinfarction cardiosclerosis. The development of postinfarction cardiosclerosis was accompanied by a decrease in myocardial excitability. The amplitude of extrasystolic contractions in the remodeled myocardium far surpassed the control. However, the amplitude of postextrasystolic contraction did not surpass that in normal contraction-relaxation cycle. Our results suggest that the ability of the sarcoplasmic reticulum in cardiomyocytes to accumulate Ca2+ is impaired during postinfarction remodeling.

[Potential of bone marrow mesenchymal stem cells for the treatment of diseases associated with damage of cardiac tissue].

Ability of mononuclear and adhesive cells to form differentiated elements of various tissues and organs in tissue culture in vitro has been studied in experiments on CBA mice. It has been established that adhesion mesenchymal stem cells are present in bone marrow. These cells are able to generate muscular, nervous, endothelioid, epithelioid, reticular, fibroblastoid, chondrogenic, osteogenic, and other types of cells. Mesenchymal islets have been frequently found both as parts of colonies and as independent units. Potential developmental flexibility of mesenchymal cells allows to suppose their high efficacy in pathogenetic cell therapy of heart diseases when besides damaged muscular elements vascular and nervous elements should be also restored. Mononuclear cells have not demonstrated this ability. They formed mainly monocyte-macrophagal and lymphoid cells.

In vitro formation of mesenchymal bone marrow islets.

We studied the formation of mesenchymal islets in the culture of bone marrow cells in vitro. Islet-like structures detected on day 6 of culturing contained a central epithelioid cell (differing from macrophages and fibroblasts) surrounded with round mesenchymal cells. The number of mesenchymal islets increased on days 12-14 of culturing, but decreased to zero by the 24th day. They appeared not only as individual structures, but also entered the composition of colonies and formed assemblies with surrounding cells of different maturity. Our results show that mesenchymal islets serve as structural and functional units of mesenchymopoiesis.

[The role of the hemopoiesis-inducing microenvironment in the postradiation regeneration of hemopoiesis]. / Rol' gemopoézindutsiruiushchego mikrookruzheniia v postluchevoi regeneratsii gemopoéza.

The dynamic of granulocytic macrophages and erythroid precursors content in bone marrow of CBA mice, irradiated by 2.0 Gy and the level of colony-stimulating and erythropoietic activities in supernatant of bone marrow myelocariocytes and blood serum were studied. The process of haemopoiesis regeneration was accompanied by increasing of the values of these indexes in bone marrow and peripheral blood. The treatment of bone marrow cells by monoclonal antibodies to Thy 1.2 antigens resulted in decreasing of myeloid precursors and diminishing of colony-stimulating activity of bone marrow cells supernatant.

[The effect of D-glucuronic acid on the regenerative processes of granulomonocytopoiesis in cytostatic-induced myelodepression]. / Vliianie D-gliukuronovoi kisloty na protsessy regeneratsii granulomonotsitopoéza pri tsitostaticheskoi mielodepressii.

Whether cytostatic-induced disorders of the blood system can be corrected with D-glucuronic acid has been studied in murine experiments. D-glucuronic acid has been demonstrated to selectively stimulate the processes of bone marrow granulomonocytopoiesis both in intact animals and in rats with bone marrow hypoplasia induced by cyclophosphanum. During D-glucuronic acid administration, stimulation of hemopoietic regenerative processes is followed by the development of granulocyte lineage hyperplasia in bone marrow, the rapid restoration of blood polymorphonuclear leukocyte and monocyte counts and the development of neutrophilia and monocytosis.

[The production by bone marrow cells of humoral factors in extreme exposures of different origins]. / Produktsiia kostnomozhgovymi kletkami gumoral'nykh faktorov pri ékstremal'nykh vozdeistviiakh razlichnogo geneza.

The intensification of cytokine-producing activity by mouse bone marrow cells forming the hemopoiesis-inducing microenvironment (HIM) was demonstrated to be an obligatory component of adaptation processes developing in the body under the influence of different extreme factors (immobilization, inflammation, cytostatics, irradiation). As a rule, the first stress reaction of adhesive and nonadhesive cells consists in interleukin-1 and interleukin-3 secretion with following erythropoietic and colony-stimulating activity induction. For all this, the levels and periods of production of hemopoiesis humoral regulators are comparable under hemopoiesis-stimulating or -suppressing influences. Finally Activation of HIM functional properties expresses the interaction of central and local regulating systems, which favours the formation of an optimal response of the blood system to stress.

[Mechanisms of the stimulating effect of d-glucuronic acid on the processes of bone marrow granulomonocytopoiesis in cytostatic myelodepression]. / O mekhanismakh stimuliruiushchego vliianie d-gliukuronovoi kisloty na protsessy kostnomozgovogo granulomonotsitopoéza v usloviiakh tsitostaticheskoi mielodepressii.

The mechanisms of regulating influence of D-glucuronic acid on granulomonocytopoiesis++ have been studied by using the model of cyclophosphamide-induced myelodepression. Increase of colony-stimulating and interleukin-1 activities production by hemopoiesis inducing microenvironment cells, the stimulation of hemopoietic islets and the different granulomonocytopoiesis precursor cells forming have been shown to be the base of activating action of D-glucuronic acid on bone marrow granulomonocytopoiesis recovery.

[The structural-functional organization of the bone marrow after lethal irradiation and the transplantation of syngeneic hematopoietic cells]. / Strukturno-funktsional'naia organizatsiia kostnogo mozga posle letal'nogo oblucheniia i transplantatsii singennykh krovetvornykh kletok.

A study was made of the content and morphology of haemopoietic islands in the bone marrow of lethally irradiated CBA mice, and their change after transplantation of syngeneic haemopoietic cells. The data obtained show that the haemopoietic islands are reconstructed in the injured haemopoietic tissue due to the donor's bone-marrow nuclears. A new type of structural and functional associations, namely, stromal haemopoietic islands, has been found.

[Influence of mast cells on the regulatory mechanisms of hemopoietic bone marrow in inflammation]. / Vliianie tuchnykh kletok na kostnomozgovye mekhanizmy reguliatsii gemopoéza pri vospalenii.

Acute infectious peritonitis simulated in mice was used to show that previous osmotic deterioration of the abdominal mast cell population significantly influenced the function of hemopoiesis-inducing microenvironment (HIM). The earlier production of the colony-stimulating and erythropoietic activities by the non-adhesive myelokaryocytes and the decreased production of these activities by the adhesive cells have been established. The results obtained evidence that mast cells modulate HIM mediating their influence on hemopoiesis under natural conditions of inflammation.

[Compensation-adaptation reactions of hemopoiesis-inducing microenvironment of bone marrow in stress]. / Kompensatorno-prisposobitel'nye reaktsii gemopoézindutsiruiushchego mikro-okruzheniia kostnogo mozga pri stresse.

The time course of compensation-adaptation reactions of bone marrow hemopoiesis-inducing microenvironment (HIM) was studied in F1 (CBA x C57BL/6) mice subjected to 10-hour immobilization. The number of macrophage and fibroblastoid colony-forming units, committed and stem precursor stroma cells responsible for HIM transport was shown to increase in the hemopoietic tissue during adaptation syndrome. HIM activation in stress was found to be macrophage- and lymphocyte-dependent process.

[Mechanism of differential effect of low dose adaptogens on the functional activity of normal and transformed cellular elements in vitro]. / K mekhanizmu differentsirovannogo vliianiia malykh doz adaptogenov na funktsional'nuiu aktivnost' normal'nykh i transformirovannykh kletochnykh élementov in vitro.

Influence of water solutions of chemically pure adaptogen--synthetic analog of Rhodiola Rosea extract phenol composition (SAR) on functional activity of hemopoietic and tumor cells of mice with Ehrlich ascite cancer was studied in vitro. The periodical character of SAR effects was shown to be different for both types of cells, and at 1 x 10(-2) and 1 x 10(-26) M concentrations simultaneous stimulation of blood marrow cells colony-forming activity and inhibition of the latter in tumor elements was revealed. Essential changes of reactions of both cell types after adding the DNA-dependent RNA polymerase blocker Actinomycin D permit to suggest SAR effects to be connected with drug influence on the membrane RNA of the target cells.