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Тhe mechanisms of differentiation of mesenchimal stem cells into the somatic cells of organs and tissues underlying embryogenesis and natural reparation processes and providing the structural and functional homeostasis of cells are considered. The data on adipogenic, osteogenic, chondrogenic, miogenic, and endothelial differentiations are given, which results in the formation of the cells of mesodermal origin in organism. The problem is discussed, how the transcription factors control each type of differentiation and participatе in them using various regulatory biomolecules, transcription factors, cytokines, and chimokins being in complicate permanent interactions and forming the integrity regulatory network. The participation in differentiation processes of a number of transcription factors (Runx2, Sox9, PPARγ, MyoD, GATA4 и GATA6) is discussed, the expression of which is under a permanent chemical control within the cellular regulatory network.

The nature and ways of isolation and cultivation in vitro of keratinocytes and fibroblasts, the main cellular components of skin to prepare a new biomedical product, tissue dermal equivalent were considered. The main attention was payed to optimization of upbuilding dermal cell biomass including selection of medium compositions and conditions of cultivation. The information was given on main parameters of cell cultures as proliferation activity, viability and phenotype of the cells. Genotoxicity of fibroblasts and biocompatibility of the cells with organic matrixes to find the optimal carrier for cellular elements of tissue dermal equivalent were studied. The composition, the process of preparation of tissue dermal equivalent and perspectives of its practical application were discussed.

The effectiveness of the use of mesenchymal stem cells (MSC) from bovine adipose tissue for the treatment of an infected wound in a cow was studied. The results of clinical studies indicate that the introduction of MSCs of adipose tissue in the wound area of the cow contributes to the rapid epithelization and restoration of the skin.

The design of novel wound dressings for chronic wound treatment is still of great importance. One of the promising approaches is application of mesenchymal stem cells (MSCs), immobilized on a flexible polymer film, for healing. In this study, blended films based on polyvinyl alcohol (PVA) and pectin with different component ratio have been prepared by solution casting method and evaluated. Physicochemical properties of the formed PVA/pectin films, including their morphology, wettability, swelling, stability, mechanical characteristics, have been studied. We demonstrated that the surface of PVA/pectin films could be modified by ultraviolet or dielectric barrier discharge plasma exposure. After both ultraviolet and plasma treatment, the hydrophilicity of PVA/pectin films increased. It has been shown that additional crosslinking of PVA/pectin films with glutaraldehyde resulted in reinforcement of their structure. MSCs were cultured on neat and modified PVA/pectin samples to evaluate the effects of film characteristics and composition on cell behavior. It has been determined that MSCs effectively adhered to glutaraldehyde-crosslinked PVA/pectin films and formed on them the monolayer culture of fibroblast-like cells. The additional modification of PVA/pectin films with collagen resulted in enhancement of MSCs adhesion. Our results show that the obtained PVA/pectin films with adhered MSCs can be suggested for potential application as a part of novel complex wound dressings.

In the present study, ultrathin poly(L-lactic acid) (PLLA) films were fabricated using the spin-coating technique. Physicochemical properties of the formed materials, including their morphology, thickness, transparency, and contact angle, have been studied. We determined that the morphology of PLLA films could be regulated by changing the polymer concentration and humidity. By altering the humidity, microporous and flat PLLA films can be fabricated. The obtained samples were subsequently used for culturing mesenchymal stem cells and fibroblasts. It has been determined that cells effectively adhered to prepared films and formed on them a monolayer culture with high viability. It has been shown that PLLA films are suitable for the entrapment of curcumin (up to 12.1 μm cm−2) and provide its sustained release in solutions isotonic to blood plasma. The obtained PLLA films appear to be prospective materials for potential application in regenerative medicine as part of cell-containing tissue engineered dressings for chronic wound treatment.

Solid (smooth) and porous films of polydimethylsiloxane (PDMS) have been obtained; the effect of their structure on the adhesion of mesenchymal stem cells (MSCs) on their surface was found. It is shown that modification of these films with a (chitosan/pectin)4 multilayer increased the efficiency of viable cell adhesion. A (3-aminopropyl)triethoxysilane–glutaraldehyde system was used to enhance the binding of the polysaccharide layer to the hydrophobic surface of PDMS. It was found that MSCs formed a monolayer culture of the fibroblast-like cells with high viability on porous PDMS modified with (chitosan/pectin)4.

Layer-by-Layer assembled polyelectrolyte films offer the opportunity to control cell attachment and behavior on solid surfaces. In the present study, multilayer films based on negatively charged biopolymers (pectin, dextran sulfate, carboxymethylcellulose) and positively charged polysaccharide chitosan or synthetic polyelectrolyte polyethyleneimine has been prepared and evaluated. Physico-chemical properties of the formed multilayer films, including their growth, morphology, wettability, stability, and mechanical properties, have been studied. We demonstrated that chitosan-containing films are characterized by the linear growth, the defect-free surface, and predominantly viscoelastic properties. When chitosan is substituted for the polyethyleneimine in the multilayer system, the properties of the formed films are significantly altered: the rigidity and surface roughness increases, the film growth acquires the exponential character. The multilayer films were subsequently used for culturing mesenchymal stem cells. It has been determined that stem cells effectively adhered to chitosan-containing films and formed on them the monolayer culture of fibroblast-like cells with high viability. Our results show that cell attachment is a complex process which is not only governed by the surface functionality because one of the key parameter effects on cell adhesion is the stiffness of polyelectrolyte multilayer films. We therefore propose our Layer-by-Layer films for applications in tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2093-2104, 2018.

Human adipose-derived mesenchymal stem cells (MSCs) can be stimulated to differentiate into hepatic cells. MSC differentiation was induced by fibroblast growth factor-4, hepatocyte growth factor, oncostatin M, and dexamethasone. The influence of quercetin on MSC hepatic differentiation in culture was assayed, and 1 or 10 μmole/L quercetin added into the induction medium enhanced the manifestation of MSC hepatic differentiation. Urea secretion, cytokeratin 19 expression, and α-fetoprotein synthesis were increased. Quercetin modulated CYP1A–cytochrome P450 activity in the differentiated cells. MSCs differentiated in the presence of quercetin exhibited higher viability and resistance to oxidative stress.

The human adipose-derived mesenchymal stem cells was shown to be hepatic differentiated under influence of inductor factors. The differentiation of MSCs was induced by fibroblast growth factor-4, hepatocyte growth factor, oncostatin M and dexamethasone. The influence of quercetin on the hepatic differentiation of MSCs in culture was investigated. The adding quercetin into induction medium (1 or 10 mmol/l) enhanced the manifestation of signs of hepatic differentiation MSCs such as urea secretion, cytokeratin 19 and a-fetoprotein synthesis. Quercetin modulating action on the CYP1A — cytochrome P450 activity in differentiated cells was found. MSCs which was differentiated in the presence of quercetin had a higher viability and resistance to oxidative stress.

The paper presents the results of experimental studies in laboratory animals with a simulated infected wound. Their treatment included the application of mesenchymal stem cells (MSCs) derived from adipose tissue. It was established that the application of MSCs was accompanied by the regeneration features of skin defects, i.e. the inflammation was cut short faster, the wound healing processes accelerated, as well as the stimulation of growth of skin appendages was observed. The received results may be used as a basis for further research and development aimed at the introduction of cellular technologies for the treatment of wound defects of various etiology into clinical practice.

The levels and rates of accumulation of porphyrins in lymphoid cells and bone marrow cells treated with exogenous 5-aminolaevulinic acid (ALA) were studied. The dependence of the quantity of porphyrins accumulated in cell on ALA concentrations in the medium had maximum at 0.7-1.0 mM ALA for all the cell types studied (splenocytes, thymocytes, peripheral blood lymphocytes and bone marrow cells). The rate of accumulation of uro-, copro- and protoporphyrins depended on cell types. The lowest and the highest levels were found in splenocytes and highest in bone marrow cells respectively. It is suggested that photodynamic therapy employing ALA is potentially dangerous for blood cells.

The influence of cytokine LIF (Leukemia Inhibitory Factor) on the viability, and proliferation of mouse R1 line embryonic stem cells (ESC) and their distribution by cell cycle stages has been investigated. LIF (5-20 ng/ml) increased growth of colonies and maintained high proliferative and pluripotent properties of R1. LIF was also involved into the inhibition of spontaneous cell differentiation and apoptotic cell death; it also decreased the rations of S/G2+M cell cycle and doubling-time of cell population.

The influence of cytokine LIF (Leukemia Inhibitory Factor) on the viability, and proliferation of mouse R1 line embryonic stem cells (ESC) and their distribution by cell cycle stages has been investigated. LIF (5-20 ng/ml) increased growth of colonies and maintained high proliferative and pluripotent properties of R1. LIF was also involved into the inhibition of spontaneous cell differentiation and apoptotic cell death; it also decreased the rations of S/G2+M cell cycle and doubling-time of cell population.