Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD.

To define the value of adhesion molecules (sVCAM-1 integrin, P-selectin, E-selectin, and L-selectin) for the prediction and evaluation of the efficiency of treatment in patients with ulcerative colitis (UC) and Crohn's disease.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Hepatocarcinogenesis is associated with deregulation of the cell signaling thus targeted therapy can decelerate HCC progression by specific inhibition of alternated signaling cascades. Sorafenib is the only multitarget drug approved for HCC treatment that blocks several crucial oncogenic signaling pathways thus suppressing tumor growth, metastasis and providing survival benefit for subset of patients sensitive to sorafenib. Compensatory activation of other tumorigenic mechanisms may lead to decrease of HCC sensitivity to sorafenib. HCC are heterogenic tumors of epithelial origin, and presence of low-differentiated subpopulations of cancer stem cells or dedifferentiated fibroblastoid cells, that are less sensitive to sorafenib due to resistance to growth-inhibitory action of the drug, promotes HCC resistance to sorafenib. Analysis of the expression profile of genes encoding tissue-specific proteins, components of cell junctions, stem cell and mesenchymal markers can reveal sorafenib-resistant populations in HCC and identify signaling pathways that reduce response to sorafenib. Identification of individual sorafenib resistance mechanisms may be useful for rational choice of an appropriate combination of targeted drugs for retardation of HCC progression and improving the efficacy of therapy

Myocardial ischemia and cardiac dysfunction have been known to follow ischemic heart disease cell therapy and laser revascularization harbors a promising potential for vascular and cardiac reparation, which is corroborated by adequate preclinical evidence. In this review we present an analysis research of mesenchymal stem cells transplantation and transmyocardial laser revascularization for myocardial repair.

The upregulation of dopaminergic neuronal differentiation is necessary for stem cell therapy in Parkinson's disease (PD). In this study, neuronal differentiation efficiency increased by more than 2 times in P19 embryonic stem cells (ESCs) induced by N-acetylcysteine (NAC) and retinoic acid (RA) as compared to RA alone, with suppressed glial differentiation. The majority of NAC-treated stem cells grafted into brains of PD mice differentiated into dopaminergic neurons and persisted well for 6 weeks. Parkinsonism was also greatly improved after grafting NAC-treated cells in comparison to cells treated with only RA. Our results strongly suggest that NAC treatment may be an effective strategy for generating stem cells fated to become dopaminergic neurons for PD clinical therapy.

Small diameter tissue engineered vascular grafts could be a potential solution to the shortage of vascular substitutes in reconstructive cardiovascular surgery. Previously, we have developed a decellularization method for human umbilical arteries, which could be used as a scaffold in vascular tissue engineering. Objective of the study was to optimize the recellelularization of decellularized scaffolds with mesenchymal stem cells. In the study, the possibility of cell growth on decellularized vessel has been shown. We also has proved that the use of perfusion-bioreactor improves the results of recellularization.

We have compared the effects of anoxia on multipotent mesenchymal stromal cells (MMSCs) preconditioned at 20 and 5 % O2. It has been shown that the lack of oxygen in the growth phase is accompanied by active cell proliferation, the decrease in their size and increasing the homogeneity of the population. At the same time, the anoxia reduced share of CD54-cells and did not change the number of cells expressing CD90 and CD73 surface markers. Preconditioning at 20% O2 increased the proliferative potential of cells, which nevertheless remained significantly, lower than that of the cells preconditioned at 5% O2. The level of lactate production was also significantly higher for cells preconditioned at 20% O2. However, the highest molar ration of lactate production and glucose consumption (Y(La/Glu)) was typical for MMSC pre-cultured at 5% O2. At anoxia, monolayer MMSCs conversely showed a decrease in this ratio by comparison with control cells and the cells cultured in growth phase. While maintaining a high level of viability under anoxia in the growth phase and in monolayer, we detected significant decrease in mitochondrial transmembrane potential. At the same time, the level of reactive oxygen species was increased only for MMSCs placed in anoxia in the active growth phase.

An adult mammal is composed of more than 200 different types of specialized somatic cells whose differentiated state remains stable over the life of the organism. For a long time it was believed that the differentiation process is irreversible, and the transition between the two types of specialized cells is impossible. The possibility of direct conversion of one differentiated cell type to another was first shown in the 80s of the last century in experiments on the conversion of fibroblasts into myoblasts by ectopic expression of the transcription factor MyoD. Surprisingly, this technology has remained unclaimed in cell biology for a long time. Interest in it revived after 200 thanks to the research of Novel Prize winner Shinya Yamanaka who has shown that a small set of transcription factors (Oct4, Sox2, Klf4 and c-Myc) is capable of restoring pluripotency in somatic cells which they lost in the process of differentiation. In 2010, using a similar strategy and the tissue-specific transcription factors Vierbuchen and coauthors showed the possibility of direct conversion of fibroblasts into neurons, i. e. the possibility of transdifferentiation of one type of somatic cells in the other. The works of these authoras were a breakthrough in the field of cell biology and gave a powerful impulse to the development of cell technologies for the needs of regenerative medicine. The present review discusses the main historical discoveries that preceded this work, evaluates the status of the problem and the progress in the development of methods for reprogramming at the moment, describes the main approaches to solving the problems of reprogramming of somatic cells into neuronal, and briefly discusses the prospect of application of reprogramming and transdifferentiation of cells for such important application areas as regenerative medicine, cell replacement therapy and drug screening.

Studies of the reaction of multipotent mesenchymal stromal cells (MMSCs) derived from human adipose tissue to oxidative stress showed that cells cultivated at 5% O2 possessed much lower resistance to hydrogen peroxide. This could be consequent to low basal activities of superoxide dismutase (SOD) and glutathione peroxidase (GP) in these cells when compared to MMSCs exposed to 20 % 02 and 1% O2. Twenty-four-hour exposure of stromal precursors in a medium containing H2O2 in a minimal concentration (LD5) stimulated an oxygen-dependent rise of the SOD activity, whereas catalase and GP concentrations did not change. Activation of the antioxidant system in response to equally a weak hypoxic (1% O2) and weak hyperoxic (20% O2) stress in vitro enhances the MMSCs resistance to H2O2.

It is indubitable that autologous transplantation of mesenchymal stromal cells (MSCs) is the golden standard for cell therapy. But also it is still in interest to explore the possibilities of allogeneic MSCs transplantation, because of their special role in lymphopoiesis, particularly in the positive selection of T-lymphocytes.

The increase in the concentration level of calprotectin in serum (ICP) in patients with inflammatory bowel disease (IBD) is closely associated with increased rates of acute phase of inflammation and combined with worsening of clinical and endoscopic disease activity. In the acute stage IBD concentration UPC hung on the degree of inflammatory activity, not localization. Test with the act is a highly sensitive method for assessing the degree of inflammatory activity and the effectiveness of therapy in IBD. After transplantation of mesenchymal stromal cells from bone marrow and standard therapy largely reduced levels SKP than selective immunosuppressive therapy with infliximab (INFL) in patients with IBD.

Male Wistar-Kyoto rats aged 22-24 months were intracerebrally transplanted with syngenic bone marrow mesenchymal stem cells (BM MSC) established from the donor aged 3-4 months and 20-22 months, respectively. Using a TV device to study microcirculation in vivo, we have established that transplantation of BM MSC from young donors increased a density of the microvascular network in the pia mater of the sensorimotor cortex in old rats approximately 1.9-fold, comparing to age-matched controls, while a density of the arteriolar compartment increased approximately 2.1-fold. Transplantation of BM MSC from old donors did not lead to the significant increase in the density of the microvascular network in the pia mater, while a density of the arteriolar compartment increased approximately 1.5-fold.

The aim of the study was to examine the histological and immunohistochemical characteristics of the thymus 5 months after the intraperitoneal administration of the carcinogen (1,2-dimethylhydrazine in the dose of 20 mg/kg once a week for 2 weeks). The study was conducted on 50 outbred albino male rats. Paraffin sections of the thymus were stained with hematoxylin-eosin and were processed by an immunohistochemical method using antibodies against CD3, CD30, CD68, synaptophysin, S-100 protein, p53, bcl-2, Ki-67, as well as against IgM and IgG. It was found that carcinogen administration resulted in the increased number of thymic cells expressing bcl-2, S-100 and Ki-67, active T-lymphocytes and thymopoietic microenvironment cells, as well as in the change of the correlation between medullary and cortical CD3(+)-thymocytes with a predominance of the latter. Thus, the malignant tumor, developing in the colon, on the one hand, inhibits the supply of the precursors of thymopoiesis to the thymus, while on the other--enhances the proliferation and differentiation of thymocytes into mature forms.

The flow cytometry becomes a more and more largely applied technique. However, the sufficient novelty of technique has no worked-out standards of diagnostic of many diseases. The lacking of external control of quality promotes development of large variety of approaches to diagnostic of diseases and impossibility to compare the study results from different laboratories. The paroxysmal night hemoglobinuria is an acquired clonal disease characterized by proliferation of stem cells with partial or total loss of expression of glykosylphosphosphatidyl inositol anchor needed to conjugate a number of surface proteins. The flow cytometry is a basic technique of detection and monitoring of clone of paroxysmal night hemoglobinuria. The article presents the results of paroxysmal night hemoglobinuria testing of 8 patients in 6 independent laboratories using flow cytometry by standard protocol recommended by the International society of clinical cytometrists (ICCS).

This article is a review of the main methods and approaches used in regulation of cell therapy products in the United States of America, Canada, European Union, Australia, Japan and South Korea. Intensive developments ofscientific and technological aspects in stem cell and tissue engineering have led to the wide use of human cells and tissues for the treatment of various diseases and injuries of organs and tissues. Drug regulatory agencies of different countries are working on implementation of a risk-based legal framework with some common features. In many countries there is a multilevel control system that assures quality and safety of used cell products. Competent authorities establish strict requirements both to safety of the products and to the implemented standards of good laboratory, manufacturing, clinical and tissue practices.

New approaches to the molecular classification of breast cancer are considered. Particular emphasis is placed on its basal-like type that belongs to the most aggressive and prognostically unfavorable forms of tumor. The origin of this type of breast cancer is the subject of intense debate in the scientific community. There are three basic theories that basal-like breast carcinoma may arise from the stem or myoepithelial cells and through dedifferentiation via epithelial-mesenchymal transformation. The theory of its origin from stem/progenitor cells is most valid and proven.

It has been noted that the integration of modern data of paleontology, comparative morphology, developmental biology, and molecular genetics forms the basis for understanding the mechanisms of evolutionary transformations of ontogeny. Paleontological and morphological evidence of the evolutionary changes in ontogeny are considered based on the data of cell and molecular biology and developmental genetics. It is shown that reorganizations of gene regulatory cascades (primarily Hox genes) play a key role in the evolution of the axial organization of animals and modifications of the limb structure of metazoans, whereas the emergence and development of new types of structures was apparently determined by the emergence of new populations of stem cells in embryogenesis (for example, neural crest cells in the evolution of vertebrates).

Transgenic tobacco plants that overexpress the ARGOS-LIKE (ARL) gene of Arabidopsis thaliana have been developed. The transgenic plants possessed increased dimensions of leaves and stem, whereas the magnitude of flowers was modified to a lesser degree. The increase in the organ dimensions was a result of stimulation of cell expansion; the cell quantity in the organ was even decreased. Ectopic expression of the ARL gene was promoted in order to increase in the level of mRNA of tobacco expansine NtEXPA5. It has been shown that the ARL gene of A. thaliana can be used to obtain transgenic plants with increased sizes of the leaves and stem.

In 1932, Burrill Bernard Crohn, Leon Ginzburg, and Gordon Oppenheimer published the paper "Regional ileitis: a pathological and clinical entity" first describing terminal ileitis that took further its name from B. Crohn. Crohn's disease (CD) is a recurring systemic inflammatory disease affecting the gastrointestinal tract (GIT) with extraintestinal manifestations and systemic immune disorders. Its etiology is unknown; the pathogenesis is associated with congenital impairments in the intestinal barrier and immune response to diversified symbiotic bacteria. The classification and the specific features of the natural history of CD are presented; the possibilities of new methods for its diagnosis and treatment are shown. Its new treatment goals are formulated; these are to achieve complete recovery of the involved bowel wall; to use confocal endoscopy, ultrasonography, magnetic resonance imaging, computed tomography, positron emission tomography, and the biomarkers C-reactive protein, fecal calprotectin, and lactoferritin. Algorithms for CD diagnosis and treatment using anticytokine agents and mesenchymal stromal stem cells are given.