The effect of dipyridamole on megakaryocytopoiesis in regenerating and stationary populations of mouse bone marrow cells has been studied by heterotopic transplantation of the bone marrow using histological, electron microscopic and biochemical techniques. It is shown that drug administration induced destruction of megakaryocytes. In megakaryocytic cytoplasm giant lipid granules were found whose growth and number increase resulted in megakaryocytes kill. Gas-liquid chromatography was used to evaluate the effect of dipyridamole on distribution of lipid fatty acids of the stationary and regenerating populations of the bone marrow cells. A marked increase of the percentage of docosahexaenoic acid was found in lipids of the stationary population. Chronic dipyridamole administration caused an increase of percentage of myristic, palmitic oleic acids, and decrease of percentage of arachidonic and eicosapentaenoic acids in lipids of regenerating bone marrow cells population.

By means of heterotopic transplantation of the bone marrow interrelations of the stromal and hemopoietic tissues of the mice bone marrow have been studied at administration of dipiridamol. Effect of the drug to the hemopoiesis is realized via stem stromal cells of the bone marrow. Under the influence of dipiridamol a focus of heterotopic hemopoiesis the osteogenic component in it is present only in 30% of cases in comparison with the control. Inhibition of the stromal component proliferation is accompanied with increasing mitotic activity of the hemopoietic elements against the background of the bone marrow cellularity decrease both in the femoral bone and in the focus of heterotopic hemopoiesis. At administration of dipiridamol a phenomenon of noneffective megakaryocytopoiesis with the intrabone marrow destruction of megakaryocytes, resulting in local release of thrombocyte growth factor, which has a compensatory character.

The construction of hematopoietic territories following heterotopic bone marrow transplantation is accompanied by transfer of the hematopoiesis-inducing microenvironment, which determines the type and volume of the developing hematopoietic tissue, and the cells transferring it are stromal cells of the hematopoietic organs [4-6]. A general feature of cells of connective-tissue nature is the presence of a receptor for platelet-secreted growth factor (PSGF), by means of which the stimulating action of PSGF on proliferative is realized [1, 10]. Blocking of platelet aggregation, leading to a decrease in the secretion of PSGF, causes inhibition of proliferative activity of connective-tissue cells.The aim of the investigation was to study the role of the stromal microenvironment in the regulation of bone-marrow hematopoiesis following administration of dipyridamole, used as a platelet disaggregant, by the method of experimental heterotopic bone marrow transplantation.

Role of the stromal microenvironment in regulation of bone marrow hemopoiesis at the administration of the thrombocyte disaggregant curantyl was studied by the method of heterotopic transplantation of the mice bone marrow. It is shown that the action of curantyl on hemopoiesis is realised through the stem stromal cells of the bone marrow. It is noted that the inhibitory action of the preparation on proliferation of osteogenic precursor-cells is followed by activation of bone resorption processes in regenerating ectopic hemopoietic organ. Under the action of curantyl at low bone marrow cellularity in the focus of heterotopic hemopoiesis and femur an increase of mitotic activity in hemopoietic elements is noted. It is revealed that a phenomenon of ineffective megakaryocytopoiesis with intramedullary destruction of megakaryocytes leads to the local excretion of the thrombocyte released growth factor (TRGF) which has a compensatory character.

Mononuclear phagocyte system (MPS) deficiency was induced by repeated peritoneal lavage in (C57Bl x CBA) F1 mice. The animals were then used as donors or recipients in heterotopic bone marrow transplantation. Yeast polysaccharide (YP) produced by Cryptococcus luteolus strain 228 was injected weekly (25 mg/kg) during 30 days after bone marrow transplantation under the kidney capsule. Bone marrow transplantation from MPC-deficient mice to intact mice 30 days later resulted in no variations from the control in cellularity and ossicle weight. YP produced an increase in cellularity, but not in ossicle weight. In the opposite experimental scheme (transplantation from intact mice to MPS-deficient mice) an increase in both cellularity and weight was not noticed. YP injections in this case resulted in the reduction of heterotopic organ size to the control level. Possible mechanisms of this phenomenon are discussed.

The effect of Cryptococcus luteolus (strain 228) heteropolysaccharide on heterotopic bone marrow organ formation was studied. Heteropolysaccharide (Hp) injections were initiated on the next day after bone marrow transplantation and were performed weekly for 30 days. This resulted in the increase in both the cellularity and the weight of the ossicle. The injections performed twice weekly produced the decrease of cellularity while ossicle weight did not change. Higher dose of Hp produced no changes in heterotopic bone marrow organ. Hp injections to donor mice did not result in any changes in heterotopic organ in bone marrow recipients. Thus, this kind of Hp was capable both of stimulating and inhibiting heterotopic bone marrow organ formation in relation to the dose and scheme of administration.

The effect of estrone injections on the heterotopic bone marrow organ formation was studied in (C57Bl X CBA)F1 mice by bone marrow shaft transplantation under the kidney capsule. Estrone injections resulted in femur marrow fibrosis, the increase in the weight of femur and heterotopic organ ossicle, drastic reduction in heterotopic organ cellularity. Depression of hemopoiesis in ectopic organ cannot be attributed to mechanical displacement of hemopoietic cells because a newly formed bone cavity under the kidney capsule was not closed. Thus, estrone had a detrimental effect on the creation of microenvironment in the heterotopic organ.

A single dose of 3H-thymidine was injected to mice maintained either on a 12-hour light-dark cycle (LD group) or on a long-term continuous light (LL group) at the peak of DNA synthetic activity in the tongue epithelium. The parameters of the circadian rhythm of cell division and mitotic cycle were studied. The LL group animals demonstrated pronounced asynchronization of the circadian rhythm of the mitotic index. At the same time the curves of the percentage of labeled cell populations in the LD and LL group animals appeared similar. The data suggest that asynchronization of the circadian rhythm of the mitotic index is linked with cell-population interrelations and the differences in the status of individual cell populations entering the mitotic cycle at varying times of the day.