The search for sources of stem/progenitor cells the use of which has a potential to affect course of ischemic heart disease and chronic heart failure is conducted nowadays in many countries. Resident cardiac stem cells (CSC) were revealed during recent years on the basis of expression of c-kit, sca-1, MDR1, and islet-1 markers. In vitro experiments demonstrated possibility of their differentiation into cardiomyocytes, smooth muscle cell and endothelial cells. Introduction of CSC in injured myocardium in animals facilitated its partial repair and short term improvement of cardiac function. This holds promise for the use of these cells in the future. In the review we have attempted to summarize literature data on resident CSC and their application for the treatment of heart diseases.

Our study involving healthy postmenopausal females established that mammographic breast tissue density was lower in cases of more intensive stimulation by glucose of reactive insulinemia and glucose-induced glyoxalase I activity in bood mononuclears as well as in women with higher concentrations of circulating CD90+stem cells. Conversely, the density tended to increase in those with higher ratio of glucose-induced generation of reactive oxygen species in mononuclears. Our data point to possible mechanisms of increased density as a breast cancer factor when concomitant with relative predominance of progenotoxic effect of glucose and lower CD90+stem cells levels which are believed by some authors to be capable of suppressing the growth of certain tumors.

The study of changes in the intracellular processes during differentiation of myoblasts into myotubules is of great importance for understanding several fundamental problems of cell biology. At first, this concerns the spatial organization of vacuolar apparatus that reflects the alterations in the properties of cell membranes, cytoskeleton elements and dynamics of vesicular transport in the course of differentiation. The distribution of acidic membrane organelles (lysosomes, late endosomes, Golgi cisternae) during the myotubule formation was revealed. It was shown that perinuclear localization of acidic organelles in myoblasts was replaced by diffuse distribution of these structures in the whole volume of myotubules. Using lipophilic fluorescent dyes, RH 414 and di-8-ANEPPS, the process of formation and dynamics of endocytic vesicles in myoblasts and myotubules was investigated. In the present work, semiconductive nanocrystals, quantum dots (QDs), conjugated with TAT-peptide, which belongs to cell-penetrating peptides, were used to characterize nonspecific endocytosis. It was shown that QDs--TAT complexes penetrate myoblasts but do not penetrate myotubules even after 24 h incubation, which might be connected with plasma membrane changes during the process of skeletal muscle differentiation.

The aim of the study was to compare the effects of neurotransplantation of cultural neural stem cells (NSC) and mesenchymal stem cells (MSC) on the rat behaviour and brain state after acute hypoxia. It was shown that development of two-way avoidance defensive conditioning in a shuttle box improved in rats-recipients with NSC, but not MSC as compared to control. Both the transplants of NSC and transplants of MSC exert neuroprotective influence on the rat brain. NSC both in vitro (before transplantation) and in vivo (on day 27 after transplantation) gave rise to all neural cell types: stem/progenitor cells, precursors of neurons and glia, neurons and glial cells. MSC population in vitro and in vivo (on day 10 after transplantation) consisted of fibroblast-like cells which were eliminated by day 20 after transplantation and were surrounded by reactive glia. We suggest that effects of NSC may be connected with their good survival and potential to differentiate into neurons and with trophic influence on the brain of recipient, whereas MSC only have possible positive trophic effect at early stages after transplantation.

Complementary interaction between the AGAMOUS and PINOID/ABRUPTUS genes was revealed. In double mutant abr ag-1, there is a significant increasing proliferation of cells of the floral meristem and formation of branching bine-like flowers. This data indicate the participation of the PID/ABR gene in limitation of proliferating stem cells of the floral meristem. The revealed increase of transcription level of WUS gene in flowers of the abr mutant, as well as distortion of auxin distribution, allows us to suggest that the PID/ABR gene controls auxin transport and participates in detection of expression domains for the WUS gene.

Comparative histological and morphometric methods were used to study the bone callus (BC) in rats 14 and 30 days after the experimental fibula fracture. Animals were infused with cell preparations of multipotent bone marrow stromal cells--BMSC (also known as multipotent mesenchymal stromal cells) in the site of injury immediately after the fracture. BMSC were cultivated in vitro under normoxic (20% O2) and hypoxic (5% O2) conditions. 14 days after the fracture, in rats that received no BMSC (control group) and in animals injected with BMSC, newly formed BC contained fibrous tissue, cartilage and reticulofibrous bone tissue (RFBT). The portion of BC, occupied by RFBT was significantly greater in rats that received BMSC grown at 5% O2, than in the other experimental groups. Thickening index of BC at day 14 was 1.3 and 1.4 times higher in animals treated with BMSC grown at 5% and 20% O2 (p < 0.05) than in rats that received no BMSC. At day 30, BC was histologically more mature in rats that received BMSC infusion than in the control group, while the restoration of the initial bone thickness was also more effective in these animals. Thus, the results of this study demonstrated that the infusion of allogeneic BMSC, expanded in vitro at different oxygen concentrations, into the site of fracture improved osteocartilaginous fragment and BC formation and bone size restoration in rats with fibula fracture.

Suppressor complex p130/E2f4 inhibits transcription of multiple genes proteins regulating cell cycle progression and induces cell cycle arrest at G0/G1 required for induction of cell differentiation in cells of many tissues in vivo and various cell lineages in vitro. We found here that, in mesenchymal stem cells, (MSC) activation of the Wnt/beta-catenin signal pathway induced by MSC coculture with the A-549 cell line or by growth in the medium containing Li+ ions, which resulted in the accumulation of active forms of the p130, E2f4 and beta-catenin, was not coupled with inhibition of cell cycle progression. Cell cycle synchronization of the MSC induced by thymidine and nocodazol was not resulted in change of the levels and phosphorylation pattern of the p130 in contrast to mouse hepatocytes and T98G cells which showed accumulation of the p130 form p1 and p2 in quiescence and form p3 under active proliferative. Antibody to p130 precipitated from extracts of MSC activated by Li+ ions beta the p130 form 2 and hyperphosphorilated beta-catenin. The results obtained suggest that Gsk3beta, p130 and beta-catenin form in MSC a complex the functional role of which may be associated with activation of differentiation not coupled to cell cycle arrest.

Comparative analysis of expression of the MyoD gene and m-cadherin in the myogenic precursor cells isolated from rats' muscular tissue on the 20th-21st day of embryogenesis, on the third to fifth day of postnatal development, and from adult animals was carried out. No significant differences in expression of the @MyoD@[ital] gene were observed. Nevertheless, we found that in contrast to myogenic cells isolated from postnatal muscular tissues, in the subpopulation of myoblasts isolated from embryonic tissues on the 20th-21st day of embryogenesis cells that were more progressive with respect to differentiation prevailed. These cells demonstrate little proliferative activity alongside with expression of m-cadherin, the protein responsible for cytoadherence, and, as a consequence, a higher rate of differentiation.

The action of three growth factors (EGF, bFGF, and PDGF) on mesenchymal stromal cell (MSC) subpopulations from mature bone marrow (BM) and rat embryo liver (EL) was investigated. These cells are plastic-adhesive and have different rates of adhesion (AC1-AC4 subpopulations). The efficiency of colony-formation, the size of colonies, and the number of early osteogenic progenitors with alkaline phosphatase activity in colonies and induced osteogenesis were analyzed. It was shown that EGF increased the number of bone marrow (BM) MSC colonies, but it had no influence on osteogenic differentiation. bFGF suppressed colony formation, but it stimulated both early and late stages of steogenesis. PDGF increased the size and the number of colonies in AC2 and AC3 subpopulations, but it stimulated only the ostegenesis terminal stage. The distinction between MSC subpopulations from two organs were found: MSC from EL had small osteogenic capacities and low sensitivity to grow factors; MSC from BM had no such characteristics. MSC subpopulations with different adhesion properties and from different tissues had compatible sensitivity to growth factors. Thus, these cells have no parent-progeny relationship.

The aim of this review is to consolidate various data about different functions of interleukin-11 (IL-11), a member of the IL-6 family. Numerous in vitro experiments have suggested a long list of IL-11 activities, including support and control of proliferation and differentiation of hematopoietic progenitors, as well as participation in osteoclastogenesis, neurogenesis and development of some other tissues. However, many of the in vitro effects of IL-11 have not been confirmed in experiments using animal models, hampering understanding of the physiological role of this cytokine. We discuss possible reasons for this apparent discrepancy between in vitro and in vivo data as well as perspectives of using conditional gene targeting to assess the role of IL-11 in ontogenesis and immune responses.

The aim of this study was a comparative analysis to the degree of stability of human epidermal cells found at different stages of differentiation to low temperatures. The effect of different subzero temperatures of liquid nitrogen vapor on keratinocytes found both in human skin fragments and as isolated cells extracted from skin fragments has been studied. The degree of stability of epidermal cells low temperatures was evaluated by their ability to form a multilayer stratum in culture; hence this phenomenon explains the survival of a sufficient amount of proliferative cells after exposure to subzero temperatures. Quantitative analysis of the ratio of epidermal stem, transitory and differentiated cells in a population of viable cells before and after exposure to low temperatures were determined using antibodies corresponding to their different stages of differentiation. The results of this research show that the stability of human epidermal cells to low temperature differs depending on their stage of differentiation both in situ and in vitro. Epidermal stem cells and transitory cells are more stable than differentiated cells.

By micronucleus (MN) assay with cytokinetic cytochalasin B block, the mean frequency of blood lymphocytes with MN has been determined in 76 Moscow inhabitants, 35 people from Obninsk and 122 from Chelyabinsk region. In contrast to the distribution of individuals on spontaneous frequency of cells with aberrations, which was shown to be binomial (Kusnetzov et al., 1980), the distribution of individuals on the spontaneous frequency of cells with MN in all three massif can be acknowledged as log-normal (chi2 test). Distribution of individuals in the joined massifs (Moscow and Obninsk inhabitants) and in the unique massif of all inspected with great reliability must be acknowledged as log-normal (0.70 and 0.86 correspondingly), but it cannot be regarded as Poisson, binomial or normal. Taking into account that log-normal distribution of children by spontaneous frequency of lymphocytes with MN has been observed by the inspection of 473 children from different kindergartens in Moscow we can make the conclusion that log-normal is regularity inherent in this type of damage of lymphocytes genome. On the contrary the distribution of individuals on induced by irradiation in vitro lymphocytes with MN frequency in most cases must be acknowledged as normal. This distribution character points out that damage appearance in the individual (genomic instability) in a single lymphocytes increases the probability of the damage appearance in another lymphocytes. We can propose that damaged stem cells lymphocyte progenitor's exchange by information with undamaged cells--the type of the bystander effect process. It can also be supposed that transmission of damage to daughter cells occurs in the time of stem cells division.

The dose dependencies of growth and cytogenetical values have been built to determine the critical level of root apical meristem damage induced by cute irradiation in the range from 2 to 20 Gr. We have analyzed the frequencies of aberrant anaphases and the aberration distribution per cell, on the one hand, and the growth of biomass, the survival and regeneration of the root meristem, on the other hand. The critical level of damage to the stem apical meristem and root of seedlings was defined as 44-48% of aberrant anaphase. Exceeding of this level leads to the launch of suicidal program through induction of multiaberrant damages and interphase cell death. It appears that competition of clones of non-aberrant cells, the cells bearing 1 and 2 damages and multiaberrant cells plays the primary role in the mechanisms of recovery. The regeneration provides full or partial restoration of the main root apical meristem. However these local processes are insufficient to restore morphogenesis and survival of seedlings in excess of the critical level damage.

The article deals with the last research project of Levon Mikhailovich Chailakhyan devoted to the role of local intercellular interactions in maintaining the pluripotency of embryonic stem cells and in the processes of their spontaneous multitissue differentiation. For performing the project, Levon Mikhailovich organized in 2008 a group of researchers from the Vavilov Institute of General Genetics of the Russian Academy of Sciences and Belozersky Research Institute of Physicochemical Biology of Lomonosov Moscow State University. In the last month of his life, Levon Mikhailovich wrote an article concerned with the first results of the work. At present the work on the project is being continued.

The basic mechanisms of regulation of Ca2+ influx in proliferating and differentiating myoblasts, in culture have been studied. The presence of L-type Ca2+ channels in proliferating myoblasts has been shown for the first time. The influx of Ca2+ through these channels was shown to be regulated by the adrenergic system. The influx of Ca2+ through L-type Ca2+ channels after the activation of the adrenergic system by the addition of adrenaline in comparison with the contribution of reticular stocks exhausted by ATP in calcium-free medium was estimated. It was shown that the Ca2+ influx in proliferating myoblasts is regulated by beta-2 adrenergic receptors whose action is mediated by adenylate cyclase through L-type calcium channels. In differentiating myoblasts, the Ca2+ influx on the activation of the adrenergic system was essentially lower than in proliferating cells. It was found that the maximum influx of Ca2+ may be reached by the exhaustion of reticular stocks.

To assess effect of continued immunization of mice from CBA line with inactivated group A streptococcal vaccine on levels of serum cytokines and number of stromal bone marrow progenitor cells in immunized mice and in heterotopic transplants after different variants of transplantation.

In the past few years it has been established that the heart contains a reservoir of stem and progenitor cells that have the ability to differentiate in vitro and in vivo toward vascular and cardiac lineages and that show cardiac regeneration potential in vivo following injection into the infracted myocardium. The aim of the present study was to characterize cardiac stem cells in the tissue of chronic left ventricular aneurism. It was shown that human c-kit positive cells were scattered in fibrous, muscle and adipose parts of aneurism tissue. C-kit positive cells localized mainly in fibrous tissue nearby large vessels, however, c-kit positive cells did not express endothelial, smooth muscle or cardiomyocyte cell markers. Co-localization experiments demonstrated that all c-kit positive cells were of non-hematopoietic origin, since they did not express markers such as CD34 and CD45. Majority of c-kit positive cells expressed MDR1, but showed no proliferation activity (Ki67). It thus appears that aneurism tissue could be an alternative source of autologous cardiac stem cells. However, their regeneration capacity should be further explored.

Cell therapy and the stem cells (SC) have become a popular topic during last time. The theme is cluttered with numerous publications of questionable reliability. Not all methods applied in praxis are founded on evidence-based research. In the abundant literature, there is a gap between the supposed SC's healing properties associated with their capability to migrate to and engraft in injured tissue, and lack of clear morphological evidence thereof. Accordingly, there is a gap between advertizing and the better part of professional literature: the former speaks about rejuvenation of tissues, and the latter explains sometimes questionable therapeutic effects by paracrine or immunomodulating mechanisms, secretion of cytokines and growth factors. However, a SC is an undifferentiated cell, and a specific and efficient paracrine function can hardly be awaited from it as compared to others, more differentiated cells. It should be noted in conclusion that the main problem with the SC and cell therapy is commercial influence. Probably, experience of some foreign countries should be studied, where moves have been made to stop the use of unproven treatments, including some stem cell therapy.

Mesenchymal stem cells (MSCs) therapy is a modern and promising approach to the treatment of cardiovascular diseases. The background of MSCs therapeutic usage was their ability to differentiate into cardiomyocytes and neuronal lineage cells. It has been experimentally proven that MSCs transplantation accelerates inflammation in the ischemic region, activates angiogenesis, prevents apoptosis and acts as a protective agent in the areas adjacent to infarction. This reduces the size of the scar and the volume of damaged tissue, restores the functioning of the injured organ, and returns the standard rates of behavioral and neurological reactions of the experimental animals.