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Biomedical subjects

M A Aleksandrova

Publications and source records attributed to M A Aleksandrova.

At least 19 recordsLinked to original sources

Functional activity of mitochondria in cultured neural precursor cells.

We studied mitochondrial transmembrane potential of neural precursor cells forming neurospheres in culture. Uneven energization of mitochondria in neurosphere cells was detected. Heterogeneity of cells by the mitochondrial potential increased with neurosphere enlargement during culturing. Decrease in the mitochondrial potential in the central cells in large spheres, presumably caused by insufficient diffusion of oxygen and nutrients, can provoke their damage and death. Population of cells with high mitochondrial potential responded to addition of the nuclear dye by a decrease in mitochondrial potential, which can indicate functioning of ABCG2 complex in these cells, characteristic of undifferentiated stem cells. These data will help to create optimum conditions for culturing of neural stem cells for the maintenance of their maximum functional and proliferative activity.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Comparative analysis of differentiation and behavior of human neural and mesenchymal stem cells in vitro and in vivo.

Comparative analysis of differentiation of human neural and mesenchymal stem cells in tissue culture and after transplantation into the brain was carried out using the same antibody set. Neural stem cells differentiated into all types of neural cells, are retained after transplantation, migrate, and form reciprocal relationships with the recipient brain. Mesenchymal stem cells were incapable of neural development under conditions of common culturing or after transplantation and retained the fibroblast-like status. Recipient filaments grew into mesenchymal stem cell transplants containing no neural cells due to local changes in the extracellular matrix at the site of transplantation.

Animals↗

[Evaluation of efficacy and safety of josamycin (Vilprafen) in the treatment of patients with community-acquired pneumonia].

Clinical and bacteriological efficacy ofjosamycin (Vilprafen), a macrolide antibiotic, was studied in 30 out- and inpatients at the age of 18 to 68 years (the average of 43.4+/-16.7 years old) with nonsevere (PORT) community-acquired pneumonia in the case histories. Josamycin was administered orally in a dose of 500 mg every 8 hours for 7 to 10 days. The treatment course was 5 to 10 days (the average of 7.7+/-1.3 days). The recovery was stated in 28 (93.3%) patients and the pathogen eradication was recorded in 16 (88.9%) patients. Moderate side effects not requiring discontinuation of the drug use were observed in 3 patients. The results of the treatment were indicative of the josamycin high efficacy in the treatment of the patients with nonsevere community-acquired pneumonia.

Adolescent↗

Characteristics of human neural stem cells in vitro and after transplantation into rat brain.

We studied the effect of culturing conditions on the fate of human neural stem cells after transplantation into rat brain. Human neural stem cells cultured in the presence of mitogens without LIF migrated along the ependyma and cerebral vessels of recipients, but to a great extent degenerated by the 20th day after transplantation. Neural stem cells cultured with LIF migrated, apart from the above mentioned pathways, in the cortex and hippocampus, well survived; proliferating cells were retained 30 days after transplantation.

Animals↗

Human fetal neural stem cells in rat brain: effects of preculturing and transplantation.

The fate of human fetal stem/progenitor cells transplanted into rat brain depends on conditions of preculturing (long or short) and state and site of transplantation. Human nestin-positive stem cells cultured according to the short protocol did not migrate into hypoxic and normal brain after transplantation, but actively migrated in damaged spinal cord. After transplantation of long-cultured cells into the brain mainly committed neuroblasts and solitary nestin-positive cells migrated from the site of transplantation into the brain.

Animals↗

In vivo and in vitro proliferative and differentiation activity of human embryonic retinal cells.

Differentiation of human embryonic retinal cells (20-22 weeks gestation) was studied using morphological, immunohistochemical, and biomolecular approaches. The retina included several regions differing by the degree of cell differentiation. Mitoses were rarely found in the marginal zone. This zone contained low differentiated cells. The central retinal area consisted of typical layers with differentiated cells. Culturing was accompanied by the formation of aggregates and neurospheres, where mitoses and progenitor or differentiated cells expressing markers of photoreceptors, neurons, and glia were found.

Cell Differentiation↗

Formation of neuroepithelial structures in culture of neural stem cells from human brain.

Dissociated fetal brain cells in a floating culture form clusters and then neurospheres, some of which contain structures shaped as cell "rosettes". The cells in these "rosettes" are arranged radially around the central cavity, in which their apical processes form desmosome-like contacts. Mitotic division of cells in the "rosettes" is associated with migration of the nuclei, similarly to division of neuroepithelial cells in the neural tube during normal embryogenesis. These cells express nestin, a marker of neural stem cells. The cells in "rosettes" found after transplantation have similar characteristics.

Brain↗

Transplantation of cultured neural cells from human fetuses into the brain of rats exposed to acute hypoxia.

Neural stem cells of human brain were cultured for a long time and successfully transplanted into the brain of rats exposed to acute hypoxia. Stem and committed cells, neuroblasts, and astrocytes were revealed in transplants by immunohistochemical assay. The transplants and brain tissue were not separated with a glial barrier. Human neuroblasts widely migrated into regions of neuronal degeneration in the host brain.

Animals↗

Human neural stem cells normalize rat behavior after hypoxia.

Transplants of cultured neural stem cells from human brain survived, retained multipotent activity, and produced a neuroprotective effect on degenerating neurons in the brain of adult rats subjected to hypoxic hypoxia. They normalized animal behavior and improved conditioning in two-way avoidance response paradigm in a shuttle box.

Animals↗

Immunohistochemical study of fetal stem/progenitor cells from human brain transplanted into traumatized spinal cord of adult rats.

Neural stem/progenitor cells from human fetal brain were grown in a tissue culture and transplanted into traumatized spinal cord of adult rats. The behavior and differentiation of transplanted cells were studied morphologically by means of histological and immunohistochemical methods and confocal microscopy. Human neural stem/progenitor cells were viable for not less than 3 months. They migrated and differentiated into neurons and glia in the traumatized spinal cord of adult rats.

Animals↗

Development of neural stem/progenitor cells from human brain by transplantation into the brains of adult rats.

The aim of the present work was to study human neural stem/progenitor cells (SPC) cultured in vitro and their potential to survive, migrate, and differentiate after transplantation into adult rat brain. SPC were extracted from the brains of nine-week human embryos and were cultured in selective medium for three weeks. Transplantation was with suspensions of cells or whole neurospheres; these were studied four weeks after transplantation into the hippocampus, striatum, and lateral ventricles of adult rats. Analysis of transplanted cells was based on various histological and immunohistological staining methods: bisbenzimide, bromodeoxyuridine, and antibodies to human nuclei, vimentin, beta-tubulin, neurofilaments, and glial fibrillar acidic protein, which allowed us to make independent assessments of their state and differentiation. Transplanted SPC from human brains survived well for one month in all areas of adult rat brain without immunosuppression. Cells from suspension transplants migrated intensely and differentiated into neurons and gliocytes. At the same time, transplants of whole neurospheres showed limited or no migration because of the development of a glial barrier.

Animals↗

Xenotransplantation of embryonic precursors of human myogenesis for the correction of dystrophinopathy in mice with hereditary muscular dystrophy.

Human embryonic myogenic precursors were transplanted into muscles of mdx mice with hereditary dystrophin-deficient muscular dystrophy. Transplantation induced the synthesis of human dystrophin. The number of dystrophin-positive fibers progressively decreased, however, some of them were preserved even 5 months after transplantation. Our results indicate that xenogeneic transplantation of embryonic myogenic precursors compensates the genetic defect in dystrophin-deficient mice.

Animals↗

[Development of human brain neural/progenitor cells after transplantation into the brain of adult rats].

The purpose of the present study was the investigation of human neural stem/progenitor cells (SPC) cultured in vitro, with special reference to their capacity for grafting, migration and differentiation after transplantation into adult rat brain. SPC were isolated from the brain of 9-week-old human embryos and were cultured in a selective medium for 3 weeks. For transplantation, cell suspension or whole neurospheres were used; they were studied 4 weeks following the transplantation in hippocampus, striatum and lateral ventricle of adult rat brain. For the analysis of transplanted SPC, various histological and immunohistochemical staining methods were applied (bisbenzidine, BrdU, antibodies against human nuclei, vimentin, beta-tubulin, neurofilaments, GFAP), that allowed an independent evaluation of their state and differentiation. Transplanted human brain SPC were shown to survive well for one month in all the areas of adult rat brain without immunosuppression. Cells from suspension transplants actively migrated and differentiated into neurons and glial cells. Meanwhile, cell migration from the transplanted whole neurospheres was limited or absent due to the formation of glial barrier.

Animals↗

Behavior of human neural progenitor cells transplanted to rat brain.

Human neural stem/progenitor cells provide a useful tool for studies of neural development and differentiation, as well as a potential means for neuroreplacement therapeutic needs in the human CNS. Stem cells isolated from developing human central nervous system of 8-12-week fetuses were transplanted to the forebrain and cerebellum of young and adult rats after 14 days of in vitro expansion. Cells were labeled by bisbenzimide prior to transplantation without immunosuppression. Recipient brains were examined 10 and 20 days after transplantation. Labeled stem cells were found in the neocortex, lateral ventricle and caudate nucleus in the forebrain, and in the molecular layer, Purkinje cell layer, and granular layer of the cerebellum. Mitotically dividing stem cells were observed in graft core, confirming their proliferative potential in new microenvironment. Engrafted cells migrate through the parenchyme of striatum, along the ventricular ependymal layer and callosal fibers, some of them reaching the opposite hemisphere. Some cells migrating along the capillaries express glial acid fibrillary protein, demonstrating their differentiation into astrocytes. Grafted cells expressing calbindin were found in the Purkinje cell layer, suggesting their differentiation into the Purkinje cells. At the same time, some grafted cells were undifferentiated and expressed vimentin. Our results demonstrate that cultured human neural stem/progenitor cells migrate and differentiate into both neurons and astrocytes after transplantation to the rat forebrain or cerebellum of young and adult rats.

Animals↗

Evaluation of progenitor cell cultures from human embryos for neurotransplantation.

Human neural stem cells (HNSCs) are used in studies of neural development and differentiation, and are regarded as an alternative source of tissue for neural transplantation in degenerative diseases. Selection and standardization of HNSC samples is an important task in research and clinical approaches. We evaluated embryonal brain matter obtained from human 8-12-week-old fetuses by means of flow cytometry on a panel including: nestin; vimentin; NeuN; GFAP; beta-tubulin III; CD56; N-Cad; OB-Cad; HLA-ABC; HLA-DR; CD34, and annexin. Samples from embryos of even the same gestation differ dramatically regarding neural cell development, their phenotype and viability. The samples containing the highest proportion of stem cells and multipotent progenitors of neural types, and the least of definitive cells and antigens of histocompatibility, were selected for further expansion in serum-free medium. Secondary phenotyping 14 days later revealed again a marked heterogeneity of the cultures. For the final culturing for 24 h in a serum-containing medium we selected only samples having following phenotype: nestin+, and vimentin+ no less than 25%; HLA-DR+ and CD34+ no more than 5%; GFAP+ no more than 10%; beta-tubulin+ no more than 20%; CD56+, N-Cad+, OB-Cad+, HLA-A,B,C+, and annexin+ no more than 15%; cell viability no less than 60%. Immunocytochemical study of selected samples proved that numerous neural stem cells, and neuro- and glioblasts necessary for transplantation were present. Our results demonstrate that the flow cytometry phenotyping allows the screening and standardization of HNSC samples for further expansion and transplantation.

Brain↗

Xenografts of embryonic nerve tissue from Drosophila neuromutants stimulate development of neural homografts in rat brain and block glial scar formation.

The influence of xenografts of Drosophila melanogaster embryonic nerve cells on the development of embryonic neurohomografts in the adult rat brain has been investigated. Embryonic nerve cells, marked with bacterial galactosidase gene (lacZ) from D. melanogaster strain with a mutation in the Delta locus, were transplanted into adult rat brain. Drosophila cells were easily identifiable in brain histological sections by X-gal staining. Xenografts survived for at least 2-3 weeks in the recipient brain after the operation to be subsequently attacked by macrophages. Importantly, no glial scar was formed around the xenograft. The addition of Drosophila embryonic nerve cells to a homograft of rat embryonic neural tissue facilitated the survival and development of this homograft by blocking the glial scar formation, stimulating vascularization of the graft area and differentiation of the implanted embryonic nerve cells.

Animals↗