The concept that stem cells form an independent subpopulations of somatic cells assumes the heterogeneity of cellular populations in adult tissues. As skin keratinocytes have natural affinity to extracellular matrix proteins, we made an attempt to reveal subpopulations of these cells depending on the time of their adhesion to substrates of collagen I and IV types and fibronectin. After selection for 10, 20 and 30 min the keratinocytes were cultivated for 24 h. The area of cell projection on a substrate and the spreading coefficient were measured (Kuzminykh, Petrov, 2004; Petrov et al., 2007). In 24 h statistically reliable morphological differences between the cells depending on the substratum were found. The size of the cells growing on collagen I type was twice as large as that of the cells cultivated on collagen IV type or in fibronectin. Irrespective of the substratum, up to 60-65% of the cells had a rounded form. The cultivation on collagens revealed the heterogeneity of keratinocytes both in the control cultures and under selection by adhesion time, while the cells grown on fibronectin behaved as a homogeneous population. These results suggest that, contrary to fibronectin, collagens stabilize some physiological states of keratinocytes corresponding to their interaction with extracellular matrix proteins in the organism.

The study of differentiation potential of multiponent stromal progenitor cells (PCs) in embryogenesis is a crucial issue for understanding their biology and role in tissue regeneration of an adult organism. In this study in monolayer culture there were investigated osteogenic and adipogenic capacities of fibroblast-like PCs derived from human fetal liver of 8-11 gestation weeks before and after exposure to cryoprotectant dimethyl sulphoxide (DMSO). It was shown that the primary suspension of human fetal liver cells included immature stromal fibroblast-like PCs which were able to be induced into osteogenic and adipogenic differentiation. A short-time exposure of freshly isolated human fetal liver cells to cryoprotectant DMSO led to altering properties of the fibroblast-like PCs. Under subculture conditions, it was found an increase in the number of fibroblast-like PCs which were able to be induced to osteogenic differentiation in vitro. The established fact of DMSO influence on the differentiation capacity of fetal fibroblast-like PCs is necessary to take into consideration while developing cryopreservation methods for stem cells.

The study is aimed to investigate the process of endothelial repair related to endothelial progenitor cells (EPC) in systemic sclerosis (SS), and analyze the role of EPC abnormalities in endothelial dysfunction and impaired angiogenesis. Correlation between EPC circulating levels, measured by flowcytometry, and peripheral vascular manifestations, cardiac involvement, carotid artery disease, Framingham risk factor score, endothelial function and morphological signs of microangiopathy is explored. Our data demonstrate, that EPC reduction with disease progression is closely linked with endothelial dysfunction and destructive microangiopathy, and significantly contribute into development of severe cardiac disease and pulmonary hypertension in SS patients.

Among the potential sources of cells for transplantation, the most promising autologous material for cell therapy and tissue engineering are multipotent mesenchymal stem cells (MMSC). The authors carried out an experiment dealing with MMSC xenotransplantation into the rabbit suprachoidal space on a model of laser retinal coagulation. For objective assessment of the magnitude and pattern of changes in the functional activity of different retinal cellular elements and the efficiency of MMSC transplantation, they performed electroretinographic and histological studies. The study indicated that MMSC transplantation into the suprachoroidal space is a safe and effective procedure for cell incorporation in order to treat retinal diseases. Electroretinography provided evidence that single MMSC transplantation better preserved the function of photoreceptors (a-wave). Histomorphometric studies demonstrated that the inserted cells stimulated reparative processes in the laser-induced damaged retina.

The objective of the experiment was to investigate the effect of liver fetal tissue transplantation (LFTT) in adult rats on the morphofunctional state of thymus as the central organ of cell-mediated (cellular) immunity. A positive impact of LFTT on the indices of age-dependent thymus involution has been established. That revealed itself in the corresponding morphological transformations of the microenvironment of thymocytes, changes in their number and composition as well as in the subpopulation composition of lymphocytes of the peripheral blood. The studies undertaken testify to the great possibilities (potentialities) of further research into the application of fetal hemopoietic tissues aimed at correcting age-dependent disorders of the cellular immunity link.

Skeletal muscle work hypertrophy is usually connected with muscle progenitor SC (satellite cells) activation with subsequent incorporation their nuclei into myofibers. Passive stretch of unloaded muscle was earlier established to prevent atrophic processes and be accompanied by enhanced protein synthesis. We hypothesized that elimination of SC proliferation capacity by gamma-irradiation would partly preavent stretched muscle fiber capability to maintain their size under condition of gravitational unloading. To assess the role of muscle progenitor (satellite) cells in development of passive stretch preventive effect SC proliferation was suppressed by local exposure to ionizing radiation (2500 Rad) and then subsequent hindlimb suspension or hindlimb suspension with concomitant passive stretch were carried out. Reduction of myofiber cross-sectional area and decrease in myo-nuclei number accompanying unloaded muscle atrophy were completely abolished by passive stretch both in irradiated and sham-treated animals. We concluded that satellite cells did not make essential contribution to passive stretch preventive action under condition of simulated weightlessness.

Dystrophin, subsarcolemmal protein communicating muscle fiber cytoskeleton to extracellular matrix, is believed to participate in mechanical signal transduction. Recent works testify possible signaling role of this protein to prevent development ofproteolytic processes accompanying muscle fiber atrophy and to stimulate the passive stretch anabolic effects. The experiment was carried out to assess the role of dystrophin in these processes. The study was performed on two months old C57 black and mdx (dystrophin-deficient) mice. Passive stretch resulted in attenuating atrophy development in two fiber types of both C57 black and mdx mice, at the same time fiber type slow-to-fast transformation did not occur in mdx soleus. We established ablatitious effect of chronic hindlimb unloading on SC proliferative activity in soleus muscle and drastic increase of proliferation under effect of passive stretch. We observed no relationship between altered dystrophin synthesis and satellite cell proliferation activity in soleus muscle under conditions of simulated microgravity and concurrent passive stretch. It is concluded that altered dystrophin synthesis partly retarded slow myofibers atrophy and had virtually no effect on passive stretch preventive action. Thus, the hypothesis about dystrophin key role in downregulation of atrophy signaling mechanisms has not found its confirmation concerning gravitational unloading atrophy.

Fibrocytes are the cells circulating in peripheral blood that synthesize a big number of various factors and take part in the start of reclaiming processes. The wound healing is a result of activity of fibrocytes. It is known that they participate in formation of hypertrophic and kelloid scars. The purpose of the present work was to research specific properties of fibrocytes in vitro. The data obtained testify that these cells really have hematopoietic origin and are undifferentiated. In this connection, while cultivating fibrocytes it is necessary to keep to some specific conditions: the use of the medium specific for stem cells and very high density of cultivation. In 10 days of culturing, the fibrocytes differentiate into fibroblasts. From the general pool of peripheral blood mononuclear cells, only fibrocytes are capable of DNA synthesis but in spite of it proliferative potential of these cells is very low.

Standard and high-risk groups of 77 children with neuroectodermal medulloblastoma were given sandwich chemotherapy. The former group was treated with high-dose chemotherapy complemented with autotransplantation of bone marrow and peripheral stem cells. The treatment proved effective: 7-year recurrence-free survival (0.66 +/- 0.05) (overall survival--0.67 +/- 0.05; recurrence-free--0.62 +/- 0.06). Sandwich chemotherapy administered in standard risk group was followed by 7-year recurrence-free survival (0.84 +/- 0.08). High-dose chemotherapy complemented with autotransplantation of bone marrow and peripheral stem cells in conjunction with high-dose chemotherapy resulted in 6-year recurrence-free survival: 0.77 +/- 0.08 in patients after high-dose chemotherapy and 0.46 +/- 0.10--without it.

Complete or partial restoration of the number of parenchymal cells is a vital part of the mechanism of maintaining tissue homeostasis and post-injury regeneration. It includes proliferation and differentiation of the resident stem cells, homing and differentiation of circulating stem cells, and, sometimes, transient dedifferentiation and amplification of the local parenchyma. Bone marrow serves as the principal storage site of the circulating stem cells. Several possible ways of circulating stem cells participation in tissue regeneration are discussed including trans-differentiation and fusion with resident cells. There is a theory of a common pool of circulating pluripotent stem cells present in the bone marrow and some other tissues and an alternative theory of several pools of tissue-specific circulating stem cells. The data obtained in this field of research are the starting point for development of cell-based technologies aimed at therapy of degenerative diseases and traumas.

The applications of nanotechnology to pharmacology are reviewed. The potential applications of biochips, nanosensors, bioreactors, neural stem cells, immune nanoparticles, biodegradable polymers, and convection-enhanced drug delivery in the diagnostics and treatment of diseases are discussed. Specific attention is given to developments in chemotherapeutic means, including advanced drug delivery systems and targeted nanotherapy, which will form the basis of the future nanomedicine. Numerous novel medicinal forms are discussed, including polymeric nanoparticles, nanotubes, micelles, liposomes, dendrimers, fullerenes, and hydrogels. In particular, highly stable glycosphyngolipid nanotubes and nanoliposomes are proposed as drug delivery systems. For this purpose, the model of stimulation of skin vasomotor reactions by nitroglycerin application is developed. The effect of nitroglycerin is shown to increase 1.5 times when used in the form of a dispersion with nanotubes as carriers and almost 2.5 times in the case of a dispersion with nanoliposomes as carriers. Nanotechnologically manufactured biologically active substances Apiton-25 (containing apis products) and Microhydrin (containing SiO 2 nanoparticles, silicon hydrogen bonds Si-H, and free negative charges for free radical neutralization) have been studied. The results indicate that both Apiton-25 and Microhydrin upon peroral administration enhance the cyclic trial performance during prolonged submaximal exercise in endurance-trained cyclists.

To evaluate expression of genes participating in regulation of hemopoietic stem cells (HSC) in the cells of stromal sublayer of bone marrow long-term cultures in patients with aplastic anemia (AA); to determine effects of parathyroid hormone (PTH) on stromal microenvironment and on its ability to maintain HSC homeostasis.

The modification of peritoneal cells derivation method proposed for the peritoneum rat, and the absolute amount of peritoneal lymphocytes, monocytes, macrophages, stem and polymorphonuclear neutrophyles, mat cells was determined. The procedure of acute 2% blood loss was found to reduce the total amount of the peritoneal cells due to depletion of lymphocytes accompanied by an increase in amount and proliferative activity of monocyte peritoneal cells, stem neutrophiles appearance in the peritoneal cavity. The subcutaneous injection of colchicine solution reduces the number of the peritoneal macrophages in normal rats, decreases the number of the monocytes, polymorphonuclear neutrophiles and led to disappearance of the stem neutrophiles on the second day of blood loss.

The Weisman's conception of germ track is considered in historical context focusing on fundamental differences among germ tracks in animals and plants. Differentiation of animal germ track cells occurrs once whereas in plant ontogenesis this process is multiply realizing (a concept of recurrent embriony). Fundamental differences in morphogenesis and embryogenesis of animals and plants as well as the differences in the properties of somatic and stem cells provide plants with special and additional modes of variability and evolution which are absent in animals.

Endothelial dysfunction and cell loss lead to atherosclerosis and its outcomes. Several recent studies suggested that endothelial progenitor cells (EPCs) play a key role in reendothelialization of injured vessels and in endogenous neovascularization of ischemic tissues. Modulation of EPCs number and functional activity or EPCs transplantation are a promising outlook for treatment of cardiovascular disease. In the present review, assessment of endothelial function, mechanisms of its impairment and role of EPCs in their correction are elucidated.

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.

Cytogenetic analysis of karyotypes of hESM01-hESM04 human embryonic stem cells and substrains derived from these strains showed that all these strains retained normal karyotype during long-term culturing. Two substrains of embryonic stem cells with chromosome aberrations indicating clonal origin of these strains were detected. The potentialities of using analysis of chromosome variability of embryonic stem cells for evaluation of predisposition of the corresponding genotypes to the formation of chromosome abnormalities are discussed.

During the recent decade the interests of specialists in experimental mammalian embryology were focused on studies of signal networks, regulatory programs, phenotype and behavior of embryonic and mesenchymal stem cells in culture, which triggered more active use of pluripotent stem cells in cell technologies. Laboratory preparation of primary induction tissue (extraembryonic endoderm, mesoderm, hypoblast, nodule, notochord, primary streak) remains impossible, but primary and secondary organizers and antagonist tissues are essential for simulation of axial development. Only in these sophisticated heterogeneous cell system will it be possible to simulate the real physiology and bioinformatics of the embryonic leaflets, their staged transformation into definitive organs. At present, mammalian and human fetal tissues remain the carriers of unique information of the middle and late embryogenesis. For this reason, functional and therapeutic activities of fetal cells and tissues are intensely studied in foreign countries; numerous banks of fetal somatic and stem cells are created. Banks of extraembryonic umbilical blood tissue have been created in Russia. However, the biological and information potentials of fetal/embryonic tissue remain not realized at the theoretical and applied levels.