Vol 14, No 1 (2019)

Hydrogels capable to optimize reparative regeneration and delivere biologically active components (drugs, cells, growth factors, gene constructs) in the implantation area are attracting increasing attention of developers due to high potential effectiveness of these medical devices and compliance of the approach with well-known medical trend - minimally invasive technologies. Hydrogels containing gene constructs have become especially relevant for clinical practice in the territory of the Eurasian Customs Union after gen-therapeutic drug and the first gene-activated bone substitute were registered in Russia. This review describes the main directions in development of gene-activated hydrogels divided into two categories: primitive and optimized ("smart”-hydrogels). In the case hydrogel scaffolds provide passive delivery of gene constructs, while the latter facilitate gene constructs to realize their mechanism of action.

This review summarizes data on the role of astrocytes in the normal brain function and disease. After ischemic injury astroglia participates in the processes of endogenous repair and helps the surviving nerve cells to regain their lost functions. The response of astrocytes to ischemia depends on the severity of the disease and can determine its further development. To date, cellular therapy is a promising strategy in the treatment of post-stroke states. Numerous studies have shown the positive effect of mesenchymal stem cells (MSC) on functional recovery after ischemic stroke. The main effect is probably associated to the ability of MSC to enhance the endogenous restoration potential of nerve tissue. Recent experimental data have demonstrated that a special role in the therapeutic effects of cell therapy belongs to astroglial cells. Further study of the interaction of MSC and astrocytes will help in the search for new approaches in the treatment of the ischemic injury consequences.

Benign tumors and tumor-like lesions of the bones are rare. At present, their diagnosis is based on radiation and pathological methods. However, the genetic etiology of this group of diseases is being actively studied in order to search for molecular markers with high diagnostic and prognostic potential.

Detection of ultrastructural distinctions of tumor cells and cell-to-cell cooperation in insulinomas and nonfunctioning neuroendocrine tumors of pancreas. Ultrastructural study of 38 insulinomas and 35 nonfunctioning neuroendocrine tumors of pancreas of the patients treated at Vishnevskiy Surgery Institute from 2010 to 2015. Insulinomas are characterized by high differentiation of intracellular organelles and specific secretory granules. In insulinomas the number of immature endocrine granules exceeded the number of mature granules. The tumor cells were often joined together and held with desmosomes ensuring very tight connection. Desmosome complexes were characterized by their extended length. Such ultrastructural changes were not followed by destruction of tumor cells. There was formation of specific syncytium-like structures consisting of cells connected by cytoplasmic channels with the common cytoplasm with cell organelles. In nonfunctioning tumors the most of the granules were distinguished by polymorphism and had no specific ultrastructure indicating the synthesized hormone. In large areas there were loss of plasmolemma integrity, up to its complete absence, which led to unification of cytoplasmic contents of the cells. Common junctions dominated in nonfunctioning tumors. Desmosomes were rare, poorly developed, and in the form of immature and reduced junctions. Complex cellular junctions are well developed in the cells, ensuring tight connection of tumor cells, reducing their invasive and metastatic potential. Nonfunctioning neuroendocrine tumors on the contrary are characterized by underdevelopment of cellular organelles and immaturity of secretory granules. Predominance of weak direct cell junctions, rupture of membranes of neighboring cells with simultaneous reduction of desmosomes facilitate the migration of individual tumor cells and formation of metastases.

Amyotrophic lateral sclerosis also known as motor neuron disease is a fatal neurodegenerative disease that manifests by degeneration of motor neurons, hypotrophy and atrophy of the muscles. The causes and pathogenesis of amyotrophic lateral sclerosis are not clear so far, the effective therapy is absent. Amyotrophic lateral sclerosis is diagnosed by clinical and neurophysiologic examination and only when over 80% of motor neurons are dead. The multiparameter flow cytometry was used to evaluate the expression of HLA-DR, CD38, CD117, CD13, CD33, CD56, CD90, CD45, CD10, CD71 in 86 samples of the mobilized hematopoietic stem cells from 54 amyotrophic lateral sclerosis cases and in 61 samples of mobilized hematopoietic stem cells from 54 healthy donors. The analysis showed differences in the hematopoietic stem cells subpopulations of amyotrophic lateral sclerosis donors as compared to those of healthy donors and allowed for the introduction of the notion of the amyotrophic lateral sclerosis-specific immu-nophenotypic profile of hematopoietic stem cells membrane antigens. The profile allows for verification of neurospecific immune insufficiency at the level of progenitor cells of the bone marrow and diagnostics of the family and sporadic amyotrophic lateral sclerosis in a molecular-biological way at the earliest stage before clinical manifestation of the disease. We suppose that the amyotrophic lateral sclerosis makes its debut as the disease of hematopoietic stem cells and manifests as pathologic changes at the level of hematopoietic stem cells genome and proteome that are represented in the subpopulation composition of hematopoietic stem cells and their immunophenotypic characteristics, becoming the cause of genetically determined genuine autoimmune origin of the disease so that the motor neuron disease manifests only in the end. However, further research with larger samples and experimental check of the evidence is required.