The paper analyzes the achievements and prospects of creating implantable cell- and tissue-engineering designs (CEDs and TEDs) of auxiliary liver to treat liver failure. Emphasizes the need to maintenance long-term and steady function of implantable CEDs and TEDs at the treatment of liver failure, by forming in them de novo hepatospecific structures and transformation of these structures in the new centers of restorative regeneration of damaged liver. CEDs and TEDs acquire these properties due to inclusion in their designs small-differentiated cells: liverspecific cells (parenchymal and non-parenchymal), cells, committed in hepatoid direction and bone marrow cells, adherent to the biocompatible and biodegradable 3D-material, simulating the properties of the extracellular matrix The article analyzes the advantages, disadvantages and prospects for using the major groups of matrices materials (biological, synthetic,inclusive biopolymer and tissue-specific composite materials, obtained by liver decellularization). Indicates that the biopolymer materials occupy a preferred place among biodegradable scaffolds as have not only biocompatible, but also the properties of biostimulants. Since the production of the TEDs requires the provision of adequate stereotypical distribution of different types of cells in the matrix is paid great attention to the production of micro-scale, medium-scale and large-scale TEDs of auxiliary liver. However, points out that none of the problems of producing TEDs liver (choice of sources and technologies to produce small-differentiated cells, the selection matrix and technology of cell-sowing, the choice of assembly technology TEDs) can not be considered definitively settled

The authors prove variants of immune reacting of an human organism in organ transplantation by existence of individual specific programs of reacting on alloantigens which, using natural activatory and inhibitory mecha- nisms, form various degree of stability of two physiological stereotypes of “behavior of immune system” – ef- fectoric and tolerogenic. For identification of an individual predominant stereotype of recipient immune reacting on a graft and for forecasting changes of an immunological homeostasis in a human organism, authors suggest to use indexes of reactance of immune system – conservatism and plasticity which can be taped by selection of the conforming biomarkers. Now the system of markers characterizing inflammatory reactions (infections/ inflammation) for recognition organ rejection and related complications, is widely used. For forecasting of an individual dominant stereotype of reacting in immunologically quiet post-transplant follow-up authors suggest to study a system of informative cellular markers of adaptive immunity and to use them for a formation of complex informative diagnostic immuno-cellular modules.

The authors prove variants of immune reacting of an human organism in organ transplantation by existence of individual speci fi c programs of reacting on alloantigens which, using natural activatory and inhibitory mecha- nisms, form various degree of stability of two physiological stereotypes of “behavior of immune system” – ef- fectoric and tolerogenic. For identi fi cation of an individual predominant stereotype of recipient immune reacting on a graft and for forecasting changes of an immunological homeostasis in a human organism, authors suggest to use indexes of reactance of immune system – conservatism and plasticity which can be taped by selection of the conforming biomarkers. Now the system of markers characterizing in fl ammatory reactions (infections/ in fl ammation) for recognition organ rejection and related complications, is widely used. For forecasting of an individual dominant stereotype of reacting in immunologically quiet post-transplant follow-up authors suggest to study a system of informative cellular markers of adaptive immunity and to use them for a formation of complex informative diagnostic immuno-cellular modules.

In this review article the necessity of adaptation and introduction into clinical practice of simultaneous monitoring of immune blood cells and cytokines in patients with grafted organs for a choice of individual tactic of immuno- suppressive therapy, determination of its efficiency and forecasting is proved. It is emphasized, that with the spe- cial attention it ought to concern to characteristic of CD4 + T-lymphocytes and to definition of an interrelation of their separate populations in peripheral blood (Treg, Th17, Tact memory cells – CD4+CD25hiCD127hiCD45RO) since they are the basic participants of immune system reaction on grafts.

Aim. To compare the effectiveness of MSC with different degree of ontogenetic maturity (MSC bone marrow – MSC BM and MSC umbilical cord – MSC UC) on regenerative processes in injured liver. Methods. In 4 groups of experiments on Wistar rats (n = 80) with a model of fibrotic toxic liver damage (FLD) it was studied the effect of MSCs with different degree of ontogenetic maturity on recovery processes at the regeneration of damaged liver: 1 gr. – Control, 2 gr. and 3 gr. introduction of MSC BM, included in Sphero®GEL-long in doses of 2.5 ×106 and 5.0 x 106 cells, respectively, and 4 gr. – introduction of MSC UC in the form of cell-spheroids (8–10 × 105 cells). The cells were injected into the damaged liver in 7 days after the end of FDL-modeling. The effect of cell therapy was studied during 180 days. The effectiveness of corrective therapy was evaluated by the results of functional and morphological investigations of livers (histological control of parenchymal and nonparenchy- mal liver tissue). Results. MSC BM in both doses and MSC UC contributed to a more rapid normalization of liver enzyme indices compared with the control (1 gr.), but the differences in the rate of recovery of disturbed enzymatic liver functions between groups 2, 3 and 4 – were absent. In 90 days after the cell application it was determined a more pronounced recovery activity of cells in groups 3 and 4; in 180 days the more pronounced activation of recovery processes was observed in group 3; but in group 4 the sclerotic processes were more pro- nounced in this period. Conclusion. For the induction of recovery processes in damage liver it is advisable not to use the MSC UC, but to use MSC BM in the Sphero®GEL, because MSC BM exert not only local but also systemic immune-regulatory effect, increasing the pool of T-reg. cells, which are additional carriers of regenera- tion information in organism.

In this article the main mechanisms and methods of immune tolerance producing under influence of different antigenic loads in organism were considered.It was shown that the state of steady tolerance was produced by making the balance of effectory and regulatory cell interactions into innate and adaptive immunities. But because of a high risk of transplant rejection at different methods of tolerance producing it is necessary to work out safe diagnostic and prognostic methods for controlling of an individual level and power tolerance stability.

In this article the necessity of working out of individual therapeutical immunosuppressive tactics was considered. The authors believe that doses and schemes of used drugs must not prevent the immunity regulation. Immunosuppressive drugs must induce native mechanisms of immune tolerance and reparative regeneration for preventing of fibrotic processes in grafts (liver).For optimal effect of drug immunosuppression after clinical liver transplantation it was suggested to reveal tolerogenic recipient's groups and also to work out and use informative diagnostic and prognostic methods for value of individual level and power tolerance stability of recipients.

It is known, transplantation of organs is accompanied by activation of adaptive immunity (cellular and humoral) and innate immunity in an organism of the recipient. Population of T-lymphocyte which includes some subpopu- lations of cells , such as Тcyt, Th1, Th2 and T-regulatory cells, first of all responsible for development of these forms of the immune answer. The actual problem of modern transplantology is working out of methods which would promote accumulation in an organism of recipient T-regulatory of cells with suppressive properties for formation the donor-specific immune tolerance into recipient`s organism.

In this review the modern conception of induction of immune tolerance was presented. Possibilities of immune tolerance induction after organs transplantation by allogenic bone marrow cells were considered.

The effect of cell transplantation into cryodamaged rat myocardium was studied on isolated hearts by increasing functional load to the left ventricle. Transplantation of allogeneic fetal cardiomyocytes improved the function of the left ventricle under conditions of considerably increased preload. Transplantation of autologous mesenchymal stem cells repaired leftventricular function under conditions of increased pre- and afterload.

We describe the possibility of obtaining cardiomyocyte-like cell cultures from rat, guinea pig, and human bone marrow stromal stem cells. The content of troponin I-positive cells attains 35-45% of the total number of cells in the cultures and persists at this level for up to 4 months under differentiation conditions. Spontaneous contractions of cardiomyocyte-like cells were observed after the formation of cell monolayer under differentiation conditions.

The effect of 24-h cold storage of liver on nucleoside transport was investigated. Nucleoside transport was estimated under conditions when both known types of nucleoside transport, facilitated diffusion and Na+/nucleoside cotransport, were active and when one of these transport mechanisms was inhibited. The rate of adenosine transport was not decreased after long-term cold storage of the liver. Inhibition of one of the transport systems decreased the rate of adenosine uptake before and after preservation of the liver to about the same extent. The adenosine transport rate was maintained during long-term (100 min) liver perfusion ex vivo. Slight activation of energy-dependent transport in the beginning of reperfusion and the slower recovery of this transport after the second transition from Na+-free to Na+-containing perfusion are not regarded as physiologically important because they were observed after changing the ionic content of the extracellular medium. We conclude that the nucleoside transport systems in liver are quite well preserved after 24-h cold storage of the organ.

The aim of the study was to elucidate the role of nucleoside transport systems in the postischemic release of nucleosides and nucleobases accumulated by the rat liver during cold storage. Livers were preserved for 24 h in Euro-Collins (EC) or in a lactobionate-based solution (LBS) without exogenous adenosine. The rates of release of uric acid, xanthine, hypoxanthine, inosine, adenosine, uridine, and cytidine were monitored during early reperfusion. The greater part of the purines and pyrimidines (up to 80%) was lost in the first 2 min of reperfusion. After storage in EC, uric acid and xanthine formed more than 90% of the total purines released; nucleosides did not exceed 5% of the total. After storage in LBS, hypoxanthine formed more than 80% of purine efflux and the release of inosine and uridine was increased 5-10 times. These changes were shown to be due to the presence of allopurinol in LBS. Dipyridamole (an inhibitor of equilibrative nucleoside transporters) decreased the efflux of uric acid after storage in EC but residual release remained high. Dipyridamole exerted the most pronounced effect on the release of nucleosides (inosine and uridine) from livers stored in LBS. The use of sodium-free media for liver preservation and reperfusion did not alter the rates of purine and pyrimidine release. We conclude that equilibrative nucleoside transporters mediate the postischemic release of nucleosides and also, but to a less degree, of uric acid. Simple diffusion is an important factor in the release of nucleobases. Active Na(+)/nucleoside cotransport does not play an important role in early reperfusion.

An isocratic, reversed-phase HPLC method was developed for the determination of the rates of purine and pyrimidine efflux during early reperfusion of isolated organs after non-perfusion cold conservation. The method enables determination of uric acid, cytidine, xanthine, hypoxanthine, uridine, AMP, inosine, and adenosine in liver perfusate using a standard C-18 column (25 cm length). Peaks are resolved by elution with buffer containing 1% acetonitrile, 20 mM potassium citrate (pH 6.25), and 25-55 mM tetramethylammonium. The effects of pH and solvents on peak retention times are described. As an example of the application of the method, the effects of allopurinol on the rates of postischemic efflux of purines and pyrimidines during reperfusion of liver stored in the cold for 24 h in Euro-Collins solution was studied.

An experimental study in 307 isolated rat hearts was concerned with variations in myocardial resting tension, resting membrane potential, ATP levels and myocardial heat production in conditions of cardioplegic heart arrest by an ion-balanced cardioplegic solution with and without phosphorylated metabolites (ATP, phosphocreatine, inosine-F, glucose-6-phosphate) and dephosphorylated metabolites (glucose, inosine, and inorganic phosphates). Phosphorylated metabolites, incorporated in the solution, had a marked protective effect due to the activation of substrate regulation mechanisms at different stages of ATP synthesis and facilitation of cardiomyocyte adaptation to ischemic, hypothermic and cardioplegic exposure.