To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006.

The work has been carried out on mice of the Tg8 line with knockout of gene of monoamineoxidase A with an increase of serotonin and noradrenaline content in the brain, and on mice of the C3H line with unchanged genome and normal concentration of monoamines. An immunocytochemical study has been performed of development of neurons producing gonadotropin-releasing hormone (GnRH) under conditions of excess of serotonin and noradrenaline in the mice in embryogenesis. The GnRH-neurons were revealed at the 18th day of embryonic development in telencephalon along trajectory of their migration from olfactory bulbs to the retrochiasmatic area. In telencephalon of mouse embryos of the Tg8 line, a redistribution of the GnRH-neurons along their migration trajectory was observed as compared with embryos of the C3H line mice. The percent of the GnRH-neurons in the Tg8 mouse embryos in caudal parts of the migration trajectory was lower than in rostral parts, the opposite distribution of the neurons being observed in the C3H line mouse embryos; at the excess of serotonin and noradrenaline in the Tg8 line mouse embryos, the total amount of GnRH-neurons in the brain was lower than in the C3H mice. In males of the Tg8 line mice under conditions of excess of serotonin and noradrenaline the optical density of neurons, which correlated with the GnRH concentration in the cell, was higher than in control mice. Thus, in the Tg8 mice under conditions of the serotonin and noradrenaline excess, migration of the GnRH-neurons to their final anlage in hypothalamus is accelerated as well as the total number of the GnRH-neurons decreases, which indicates a decrease of proliferation of cells-precursors and the earlier differentiation of neurons.

The experiments on 29 white non-inbred rats with chronic renal failure (CRF) induced by right-side nephrectomy and coagulation of 1/2-2/3 of parenchyma of the left kidney were made to study the trend in renal function after injection (into renal cortex or intravenously) of cultured stem or progenitor cells from human fetuses (total culture of fetal kidney or mesenchymal stem cells of the bone marrow). In control tests with salt solution functional indices reflected persistence of CRF. On day 4 after introduction of the fetal cells into renal parenchyma renal function improved and normalized in 2 weeks. After intravenous injection of fetal cells CRF reduced slowly, especially after injection of medullary mesenchymal cells with normalization in 1 month. 2.5-3.5 months after the injection test parameters in some rats deteriorated but remained close to normal values. Glomerular filtration after injection of stem and progenitor cells recovered better while canalicular sodium reabsorption underwent normalization but was followed by deterioration.

This review paper describes the evolution of the ideas of periodontal tissue regeneration, starting with the concept of selective cellular repopulation, stimulation of resident precursor cells in the regeneration focus, up to the application of versatile potential of the stromal stem cells (SSC). Effects of stem cells isolated from an embryo, bone marrow, and adipose tissue, are described, as well as the immunophenotype of freshly isolated SSC, that of precultured vascular cell fraction as compared with the immunophenotype of SSC cultured during various time periods. The results of the study of the processes of proliferation and cell differentiation of SSC transplanted into the deep periodontal defects, are analyzed using proliferating cell nuclear antigen (PCNA) and green fluorescent protein. During the process of regeneration, the interaction of transplanted SSC with the local microenvironment is mediated by special membranous cell receptors. The coordination of cell behavior by means of adhesive and communicative contacts which provide a signal platform for the control of cellular functions, is discussed.

to study of intramyocardial implantation of cultured bone marrow stem cells on myocardial perfusion and contractility in the surgical treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF), by synchronized single-photon emission computed tomography (SSPECT) of the myocardium.

Murine embryonic stem cells (mESC) are capable of unlimiting proliferation with maintenance of pluripotency during long-term cultivation. Signaling pathways regulating the cell cycle of mESC are of the great interest for further investigation. This review concerns to the cell cycle regulation of mESC through different signaling pathways (LIF-STAT3, PI3K-Akt, Wnt-beta-catenin) and to the mechanisms of unlimited proliferation of mESC and their inability to undergo long-term block of proliferation in response to DNA-damaging and stress factors. The functioning of negative cell cycle regulators (cyclin-kinase inhibitors and Rb) and positive cell cycle regulators (cyclin-kinase complexes and E2F factors) are also topics of this review. It is considered that, permanent mitogenic stimuli are needed to prevent induction of apoptosis. Therefore, the agents which cause prolonged halt of proliferation without ongoing onset of differentiation or induction of apoptosis are currently unknown. The main focus is given to the role of the Wnt signaling pathway in sustaining the pluripotent state of mESC. The cell cycle regulation by downstream targets of LIF-STAT3, PI3-kinase and Wnt-beta-catenin pathways is discussed in light of cooperative action of these pathways for maintenance of undifferentiated state of mESC.

A combined cellular transplant for injection has been designed, by using lowly differentiated stromal fat tissue cells obtained from Wistar rats and it preserved biological and physical properties after passing through a small-diameter injection needle (an insulin syringe). A morphological study of the results of its transplantation into paraurethral tissues in 28 female rats showed that the transplant cells, autologous ones in particular, activated the proliferation of local connective tissue cell populations and retained their viability and proliferative and synthetic activities up 20 days or more. At the end of the experiment (on days 27-35), marked focal connective tissue enlargement at the site of injection of both allo- and autografts results in the narrowing of the urethral lumen. The injection implantation of combined allo- and autografts opens up new avenues for the treatment of pathological processes of the reproductive and urinary tracts.

The results of in situ hybridization with labeled species specific and X-chromosome-specific probes suggest that hybrid cells obtained by fusion of Mus musculus embryonic stem cells (genotype XY) and splenocytes of M. caroli females contain two parental X-chromosomes. In five clones of hybrid cells, differentiation was induced in embryoid bodies in vitro, which was accompanied by inactivation of one of X-chromosomes. We analyzed the expression of Xist and Gla alleles in the embryoid bodies using RT-PCR with an account that expression of locus Xist is one of key events in X-chromosome inactivation, while gene Gla was used as a marker of active X-chromosome. Identification of allele transcripts of loci Xist and Gla was based on restriction polymorphism between M. musculus and M. caroli that we had described. Transcripts of both parental alleles of loci Xist and Gla were present in the embryoid bodies of all studied hybrid clones. No preferential inactivation of M. musculus or M. caroli X-chromosome was found in the tested embryonic hybrid cells despite the initial differences in ontogenetic status between X-chromosomes of embryonic stem cells and splenocytes.

Testicular tumors illustrate curable cancer, but 25% patients are resistant to standard therapy. High-dose chemotherapy (HDC) is promising therapy for germ-cell tumors with poor prognosis. HDC and transplantation of autologous stem cells were performed in 13 patients with germ-cell testicular tumors (GTT). In 6 patients of group 1 HDC was first-line treatment in poor prognosis, in 7 patients (group 2) it was a salvage treatment after recurrences. Patients of group 1 had longer mean survival than those of group 2 (31.3 and 11 months, respectively; p = 0.136). Two patients died of HDC complications. Neurological, hematological and other complications occurred. In spite of 50-90% remission after HDC, multicenter prospective randomized trials will give final conclusion on effectiveness of HDC which must be performed in special clinics having many specialists in their staff (urologists, oncologists, chemotherapists, etc.).

This review describes the most recent data on an intermediate filament protein nestin, which is regarded by most of the authors as a possible neural stem/progenitor cells marker. Several structure-functional characteristics of nestin, its occurrence in different cell types at various stages of ontogenesis in physiological and pathological conditions are reviewed.

Nestin, an intermediate filament protein, is known to be expressed in the proliferating and provisional cells of the developing mammalian brain and is lost during differentiation. The aim of the present study was to determine the morphological type and localization areas of the rat brain cells exhibiting the ability to synthesize nestin after a short-term global ischemia of the brain. Induction of nestin synthesis after a short-term ischemia was found within the injured brain areas in astrocytes, which exhibited structural features atypical for these cells in mature brain and maintained them for a long time, and in the morphologically undifferentiated cells of subventricular zone, which were able to proliferate. However, acquisition by astrocytes of some phenotypic properties of immature glial cell does not by itself support the view that they may transform into neural stem cells.

Imunophenotic characteristic of the mesenchymal stem and progenitor cells, their tissue origin and functional peculiarities as well as immunological aspects of its transplantation are presented in the article. Also the address migration and the site-specific differentiation of mesenchymal stem cells its age-related and pathological process induced changes are discussed. Prospects of clinical use of mesenchymal stem cells for the treatment of degenerative arthritis, spinal cord injuries, myocardial infarction and other disorders are shown.

The concept of paragenome is proposed, which is considered as a transient array of short DNA molecules appearing on the chromosome surface during development for the control of genome. The paragenome consists of printomeres, chronomeres, and phylomeres. Chronomeres and printomeres are obligatory for cells of certain differentiation lineages, but the cells of different lineages differ in the sets of these organelles. Phylomeres are facultative, since they appear only when development is modified. The paragenome is a system governing the chromatin configuration and level of structural genes expression, ensuring the interpretation of positional information by the cells and their differentiation in regulatory morphogenesis, and controlling the development in time. Deciphering of the paragenome will allow realization in future of direct reprogramming of somatic cell nuclei without using stem cells and eggs.

Specific factors that determine the cell fate in early embryogenesis are modulated during interaction of signaling pathways to form a unique regulatory network inside the cell, which is essential for differentiation of various cell populations. We carried out a comparative study of expression of the genes of TGFbeta growth factors and their receptors at the initial stages of differentiation of the embryonic stem cells, during formation of spheroids of the embryonic teratocarcinoma cells, and during growth of neoplastic cells in vivo in immunodeficient mice. The patterns of expression of the genes Activin, Nodal, Lefty1, Lefty2, BMP, and TGF1 and their receptors ActRI, ActRII, BMPRI, TGFbeta1R1, and Tdgf proved to be identical. Expression of alpha-fetoprotein and transcription factor Gata4 protein, specific for the primary endoderm, was detected in the embryonic teratocarcinoma cells. In Undifferentiated embryonic stem cells, expression of Gata4 was found at the mRNA level, while expression at the level of proteins appeared only in the primary endoderm cells in the embryoid bodies. The results obtained suggest that despite the existence of similar signaling systems in the embryonic stem and teratocarcinoma cells, the presence of different intracellular specific factors forms radically different regulatory pathways, which determine the program of their differentiation.

Clones of telomerized fibroblasts of adult human skin have earlier been obtained. It was shown that despite their fast growth in mass cultures, these cells poorly form colonies. Conditioned medium, antioxidants, and reduced partial oxygen pressure enhanced their colony formation, but not to the level characteristic of the initial cells. The conditioned medium of telomerized cells enhanced colony formation to a much greater extent than that of the initial cells. A study of proteome of the telomerized fibroblasts has revealed changes in the activities of tens of genes. A general trend consists in weakening and increased lability of the cytoskeleton and in activation of the mechanisms controlling protein degradation. However, these changes are not very pronounced. During the formation of immortal telomerized cells, selection takes place, which appears to determine changes in the expression of some genes. It was proposed that a decrease in the capacity of telomerized cells for colony formation is due to increased requirements of these cells to cell-cell contacts. The rate of cell growth reached that characteristic of mass cultures only in the largest colonies. In this respect, the telomerized fibroblasts resembled stem cells: they are capable of self-maintenance, but “escape” to differentiation in the absence of the corresponding microenvironment (niche), which is represented by other fibroblasts. Nondividing cells in the test of colony formation should be regarded as differentiated cells, since they have no features of degradation, preserve their viability, actively move, grow, phagocytize debris, etc. It was also shown that telomerization did not prevent differentiation of myoblasts and human neural stem cells. Thus, the results obtained suggest the existence of normal mechanisms underlying the regulation of proliferation in the telomerized cells, which opens possibilities of their use in cell therapy, especially in the case of auto-transplantation to senior people, when the cell proliferative potential is markedly reduced and accessibility of stem cells is significantly restricted.

Bone marrow stroma contains mesenchymal stem cells (MSC) which are precursor for at least mesenchyma-derived cells. Recent investigations revealed a lot of questions concerning MSC biology that should be further refined. The aim of this study was the comparative analysis of rat bone marrow stroma cells cultures. Mesenchymal precursor cells isolated from rat bone marrow were passed up to 50 times. Comparative morphological and immunophenotypical analysis of these cultures was carried out as well as their ability to osteogenic differentiation was studied. The isolated cultures contained morphologically different types of cells and thus showed a high heterogenity level. Morphology of these cell types was described. The heterogeneity level was reported to decrease over time. It was found out that subcultures isolated from different rats shared the same immunophenotype characteristics (CD90+, CD44+, CD54+, CD 106+, CD45-, CD11b-), but differed in their morphology as well as in ability to osteogenic differentiation. Thus MSC identification requires more specific marker and functional tests to be used.

The work is devoted to consequent expression of different cell types' protein markers such as vimentin, desmin, cytokeratins 7, 18, 19, stem cell markers CD34 and Bcl-2 at early stages of human prenatal development. Desmin was revealed in sinusoidal liver cells on 3.5-12 weeks of gestation, in mesenchymal cells of ventral mesentery and hepatoblasts on the 4-7 accordingly. During hepatic period of blood formation such desmin positive sinusoidal cells were found to be located close to blood cells. So called "cholangio-" cytokeratins 7 and 19 showed different expression, the first one was found only in cholangiocytes, while cytokeratin 19 existed in hepatoblasts as well until week 15-16 of prenatal development. Mesenchymal cells of ventral mesentery are positive for cytokeratins 18 and 19 even brighter than hepatoblasts in the 4-7 weeks of gestation. Bcl-2 expression was seen in the same periods in most sinusoidal and mesenchymal cells of ventral mesentery. CD34 positive cells are strongly depicted in liver sinusoids from 4th until 9th weeks of gestation, but probably they are not a source of hepatocytes' development in embryonic ontogenesis. Ventral mesentery mesenchyme was negative for this very marker. These results let us suppose that hepatocytes and cholangiocytes may develop from quite different embryonic sources: cholangyocytes grow exceptionally from duodenum epithelial cells, while there is a strong possibility that hepatoblasts formation occurs with participation of mesenchymal cells.

Cardiac cells possess limited ability to regeneration. Therefore acute myocardial infarction results in replacement of "perished" cardiomyocytes by scar tissue. The consequence of this is lowering of myocardial contractile function and development of heart failure. Novel approach to improvement of blood supply, contractility and possibly heart failure prevention--transplantation of stem cells--has attracted increasing attention during recent years. The use of autologous bone marrow stem cells is one of most perspective directions of cellular therapy. Until present time mechanism of action of stem cells, necessary amount of cellular material, most adequate method of stem cells introduction, methods of diagnosis of clinical efficacy of cellular therapy have not been fully elucidated.

We studied the effects of mesenchymal stem cells on rejection of xenogenic bone transplant. Experiments were carried out on Wistar-Kyoto rats transplanted chicken demineralized bone matrix populated or not populated with mesenchymal stem cells to the site of parietal bone defect. Histological analysis showed complete resorption of the xenogenic transplant not populated with mesenchymal stem cells by day 119. In experimental animals chicken matrix without signs of tissue inflammation was in fact completely retained over the entire period of observation. Numerous new vessels, mineralization fields, and areas of bone tissue formation were seen in the transplant.