Objective: to monitor the current trends and developments in organ donation and transplantation in the Russian Federation based on the 2020 data.

Materials and methods. Heads of organ transplant centers were surveyed through questionnaires. Data control was done using the information accounting system of the Russian Ministry of Health. Between separate federal subjects of the Russian Federation and between transplantation centers, comparative analysis of data obtained over years was performed.

Results. Based on data retrieved from the 2020 Registry, 44 kidney, 29 liver and 16 heart transplantation programs were functioning in the Russian Federation in 2020. The kidney transplant waitlist in 2020 included about 11.5% of the total 60,000 patients receiving dialysis. Organ donation activity in 2020 was 3.9 per million population, with a 74.6% multi-organ procurement rate and an average of 2.9 organs being procured from one effective donor. In 2020, there were 7.7 kidney transplants per million population, 3.8 liver transplants per million population and 1.7 heart transplants per million population. Same year, the number of transplant surgeries performed in the Russian Federation fell by 19.2% to 13.4 per million population against the background of the outbreak caused by the new coronavirus disease COVID-19. The city of Moscow and the Moscow region in 2020 accounted for 13 out of the 14 functioning organ transplantation centers, performing 66.3% of all kidney transplants and 72.4% of all extrarenal transplants in the country. The number of organ recipients in the Russian Federation have exceeded 130 per million population.

Conclusion. In 2020, despite the new coronavirus disease COVID-19 pandemic and accompanying restrictive measures, transplant centers continued to perform organ transplants, run a waiting list and monitor organ recipients. However, the number of effective donors (–22.9%) and organ transplants (–19.2%) decreased, tentatively to the 2017 levels. In 2021, transplant centers with support from health authorities will have to restore the volume of transplant care with consideration to the real needs of the population and the donor resource. The COVID-19 factor, including vaccination of the population, as well as financial support to transplantation programs, will be decisive in shaping the trend of transplantation care and organ donation in the federal subjects of the Russian Federation in the coming 1–2 years.

Introduction. In megacities, the use of organs obtained from those who died as a result of sudden out-of-hospital cardiac arrest (OHCA) for transplantation is one of the promising ways of addressing the problem of organ donor shortage. In St. Petersburg, the model of transition from life support via extracorporeal membrane oxygenation (ECMO) of patients after OHCA to ECMO life support for organs of potential donors was tested for the first time.

Materials and methods. In order to implement the program, round-the-clock ECMO and transplantation teams were organized at the inpatient emergency ward of Pavlov First St. Petersburg State Medical University. Interaction with the St. Petersburg City Emergency Station, St. Petersburg was established. The protocol of work with potential donors brought to the hospital after a sudden circulatory arrest was developed, approved by the ethics committee, and implemented in clinical practice. This was the first in Russia and in international practice. Between 2017 and 2020, 67 patients with sudden OHCA were brought to the inpatient emergency ward. In 4 (5.97%) cases, advanced cardiovascular life support was successful, and 11 (16.42%) patients became effective donors. Mortality among this group of patients without subsequent postmortem donation was 77.61% (52 patients).

Results. Liver transplantation from non-heart-beating donors (NHBDs) whose blood circulation was restored by ECMO (ECMO NHBD) was performed in 5 recipients who were in severe condition against the background of liver failure. In 1 (20%) case, there was severe liver allograft dysfunction for 33 days with subsequent complete restoration of function. Kidney transplantation was performed in 22 patients. Immediate graft function occurred in 10 (45.45%), while delayed function occurred in 12 (54.55%) patients. Kidney graft survival was 86.4%, kidney graft recipient survival was 95.5%, liver graft recipient survival was 80%, and the follow-up period was 24.1 ± 7.15 months.

Conclusion. The use of ECMO to save the lives of patients with sudden OHCA can be implemented in conditions of a high degree of organization and synchronization of the work of the city emergency medical station and the emergency department of a multidisciplinary hospital. If cardiopulmonary resuscitation with ECMO (ECMO CPR) fails, it is possible to launch the ECMO NHBD donor program. Long-term outcomes of liver and kidney transplantation from ECMO NHBD are consistent with those using organs from brain-dead donors. Widespread implementation of the new organ donation model will increase the availability of transplant care.

Back ground. Liver transplantation is an effective treatment for acute or chronic liver failure and metabolic liver disease, which is associated with good quality of life in over 80 percent of recipients. We aimed to evaluate outcome of duct-to-duct vs. Roux-en-Y hepaticojejunostomy biliary anastomoses in pediatric liver transplant recipients below 15-kg.

Methods. In this single-center retrospective study, all children less than 15 kg that have undergone liver transplantation at Nemazee Hospital Organ Transplant Center affiliated with Shiraz University of Medical Sciences from 2009 till 2019, were enrolled. Over a 10-yr period, 181 liver transplants were performed in patients with two techniques including duct-to-duct (Group 1) vs. Roux-en-Y hepaticojejunostomy biliary anastomoses (Group 2). All data was collected from patients’ medical records, operative notes, and post-transplant follow up notes. Data was analyzed by SPSS software V21.

Results. Overall, 94 patients had duct to duct anastomosis (group 1) and 87 cases had Roux-en-Y hepaticojejunostomy (group 2). The mean age of the patients was 2.46 ± 1.5. The most common underlying diseases was biliary atresia (32%). The most prevalent complication after the surgery was infection in both groups. cardiopulmonary problems were significantly higher in group 2 (24.1% vs 4.3%) (p < 0.001). The rate of infection was significantly higher in group 2, as well.

Conclusion. Our study showed a relatively high rate of post-operative infection which was the most among patients who had undergone Roux-en-Y hepaticojejunostomy. Except from biliary complications which were mostly observed in DD group, other complications were more common among Roux-en-Y group.

Treatment of ureteral strictures in the long-term post-transplant period is a complex surgical procedure. We present successful clinical cases of developed laparoscopic ureteral stricture reconstruction methods at three levels (in the pelvis, along the ureter, in the anastomosis area). These methods have shown their clinical efficacy: they are less traumatic, there are no adverse events in the early and long-term postoperative periods, and there is accelerated rehabilitation of recipients after surgery.

Background. In young children, the most common liver disease leading to transplantation is biliary atresia. Liver transplantation has fundamentally improved the survival rate of children with biliary atresia. Studies on developmental outcomes in children are mostly limited to small samples; there are no such studies in the Russian Federation.

Objective: to determine the cognitive outcomes in children undergoing one-stage or two-stage surgical treatment of biliary atresia.

Materials and Methods. 83 children were divided into groups: 36 children underwent transplantation without previous surgical interventions (group 1), 47 children underwent the Kasai palliative portoenterostomy (group 2). Inclusion criteria: 24 months of age or younger at the moment of transplantation, no medical history of neurological pathology. All children were examined before transplantation and at 1, 3, 6 and 12 months after liver transplantation. Psychomotor development was assessed using the Griffiths Psychomotor Development Scale for children under 24 months (translated by E.S. Keshishian), the Griffiths Intellectual Development Scale for children aged 2 to 8 years, and the Modified Checklist for Autism in Toddlers, Revised, for children 16-30 months old.

Results. All children had developmental delays at the time of transplantation. Up to 50% of the children had signs of cachexia, with a shoulder circumference of less than 3 percentile. Only two children showed obvious hepatic encephalopathy in the form of depressed consciousness. After liver transplantation, 94% of group 1 children recovered their preoperative psychomotor development levels, and only 68% in group 2 made these gains. At 3 and 6 months after transplantation, about 80% of group 1 children showed normal psychomotor development, whereas in group 2, only 61% did. By 12 months after liver transplantation, the difference between the groups was more evident: 83.3% of group 1 children and only 53.2% of group 2 children were developing according to age. The difference between the groups was statistically significant (p < 0.05).

Conclusion. Children who received one-stage treatment of biliary atresia and underwent liver transplantation have better neuropsychological development within a year after surgery than children with two-stage surgical treatment.

Myocardial fibrosis plays a key role in the pathogenesis of heart failure. A family of small non-coding signaling molecules, microRNAs (miRNAs), has been identified as promising profibrogenic biomarkers capable of signaling a possible risk of adverse events after heart transplantation.

Objective: to identify and evaluate the diagnostic significance of miRNAs, as well as comprehensive miRNA-based tests in heart recipients with graft myocardial fibrosis.

Materials and Methods. The study included 83 heart recipients aged 16 to 64 (48.4 ± 13.1) years. The expression levels of five microRNAs (miR-27, -101, -142, -339, -424) in venous blood plasma were measured by quantitative real-time polymerase chain reaction; galectin-3 serum levels were determined by enzyme immunoassay.

Results. Morphological signs of graft myocardial fibrosis were verified in 48 recipients. The miR-27 and miR-339 expression levels were significantly higher in heart recipients with myocardial fibrosis than in those without myocardial fibrosis (p = 0.018 and p = 0.043, respectively). Diagnostically significant threshold levels of miR-27 and miR-339 for detection of myocardial fibrosis in heart transplant recipients were determined (–4.33 and –5.24 units, respectively). The relative risk of detecting graft myocardial fibrosis in recipients with miR-27 expression value above the threshold level was RR = 1.5 ± 0.157 [95% CI 1.104-2.039], p = 0.009; for miR-339, RR = 1.31 ± 0.130 [95% CI 1.018-1.692], p = 0.036. When miR-27 expression levels and galectin-3 serum levels simultaneously exceeded their estimated thresholds, the risk of transplanted heart myocardial fibrosis increased to RR = 2.7 ± 0.456 [95% CI 1.090-6.524], p = 0.032; when miR-339 and galectin-3 simultaneously exceeded threshold values, the risk was RR = 2.0 ± 0.316 [95% CI 1.076-3.717], p = 0.028).

Conclusion. The miR-27 and miR-339 expression levels are associated with the presence of fibrotic changes in the graft myocardium. The combination of molecular-genetic and proteomic biomarkers in one test improves the diagnostic characteristics of these expressions with respect to post-transplant complications in heart recipients.

Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases. However, the number of transplant surgeries performed is not much. This is down to the high requirements on the condition of a potential lung donor and directly on the quality of the donor lung. This has significantly limited the number of optimal donors. Rehabilitation of donor lungs to optimal gas exchange indicators can be achieved and objectively assessed in the course of ex vivo lung perfusion (EVLP). The EVLP procedure is widespread in leading transplantation centers in Europe and North America. It allows to significantly expand the pool of donor lungs, thereby serving a greater number of patients in need of lung transplantation. The possibility of EVLP procedure using publicly available perfusion equipment was demonstrated. The optimized protocol fully demonstrated its reliability and efficiency. The developed perfusion solution had no statistically significant differences in comparison with the Steen SolutionTM, which in the future will serve as an alternative for EVLP procedure.

In terms of method of production, collagen carriers are subdivided into materials obtained on the basis of extracellular matrix (ECM) components, particularly collagen-containing hydrogels and decellularized tissue.

Objective: to compare in vitro the ability of biopolymer microheterogeneous collagen-containing hydrogel (BMCH) and tissue-specific matrix from decellularized porcine articular cartilage (DPAC) to support adhesion, proliferation and chondrogenic differentiation of human adipose-derived mesenchymal stem cells (hAMSCs).

Materials and methods. For cartilage decellularization, we carried out treatment with surfactants (sodium dodecyl sulfate, Triton X-100) followed by exposure in DNAase. The metabolic activity of hAMSCs was assessed by PrestoBlue™ (Invitrogen, USA) staining. The morphological study of cell-engineered constructs (CECs) formed by culturing hAMSCs in the presence of matrices was performed using histological staining and scanning electron microscopy (SEM) with lanthanide contrasting.

Results. The number of cells on the surface of both BMCH and DPAC increased within 14 days. Mitochondrial activity of the cells was 1.7, 1.7, and 1.3 times higher on days 3, 10, and 14 when cultured on DPAC compared to BMCH, respectively. On day 14 of cultivation in the chondrogenic culture medium, hAMSCs formed cell layers on the DPAC surface and on the BMCH surface. Cytoplasm of the cells included numerous granules, which, when stained, resembled the matrix itself. On the DPAC matrix surface, cells were more evenly distributed, whereas in the case of BMCH, cell adhesion and proliferation were observed only in certain areas. The ECM produced by the cells contained collagen and glycosaminoglycans (GAGs).

Conclusion. The ability of DPAC obtained according to the developed protocol to form CECs with hAMSCs with uniform distribution of cells and their production of specific collagen- and GAG-containing ECM suggests that DPAC is effective in regeneration of damaged cartilage. Chondrogenic differentiation of hAMSCs was observed both when cultured with BMCH and with DPAC. When creating a tissue equivalent of cartilage in vitro, the advantage of using tissue-specific matrix over BMCH should be considered.

Objective: to create a cell-populated small-diameter vascular graft (SDVG) using autologous endothelial cells and extracellular matrix proteins, and to evaluate the efficiency of endothelial cell monolayer formation during shear stress preconditioning in a SDVG.

Materials and methods. PHBV/PCL tubular scaffolds of vascular grafts were made by electrospinning from a mixture of polyhydroxybutyrate-valerate (PHBV) copolymer and polycaprolactone (PCL) and modified with fibrin. To populate the graft, an endothelial cell culture was isolated from the blood of patients with coronary heart disease. Phenotyping of endothelial colony-forming cell (ECFC) culture was performed by flow cytometry and immunofluorescence microscopy. Cell proliferative and angiogenic activity were also studied. Cell-populated vascular scaffolds were cultured in a pulsatile flow setup with a final shear stress of 2.85 dyne/cm². The effect of pulsatile flow on monolayer formation was assessed by immunofluorescence, scanning electron microscopy, atomic force microscopy, and whole-transcriptome RNA sequencing.

Results. Under the influence of pulsatile flow, endothelial cells that were seeded into the tubular scaffold showed an increase in the expression level of endothelial profile proteins, focal adhesion and cytoskeleton. In contrast to endothelial cell culture on a vascular graft surface under static conditions, when cultured under pulsatile flow with 2.85 dyne/ cm² shear stress, endothelial lining cells have an increased ability to adhere and are oriented along the pulsatile flow path. Whole-transcriptome RNA sequencing showed that induced shear stress increased expression levels of differentially expressed genes encoding proteins that ensure vascular development, endothelial integrity, and endothelial metabolism. A protocol for fabrication of a personalized cell-populated biodegradable SDVG under pulsatile flow conditions was developed.

Conclusion. The use of autologous fibrin and ECFC culture, as well as shear stress preconditioning, allow to obtain a personalized cell-populated SDVG with continuous functional endothelial monolayer adapted to the flow.

Objective: to study cellular and lipid infiltration, as well as the expression of tissue inhibitors of metalloproteinases (TIMP) types 1 and 2 in biological prosthetic heart valves (BPHVs) explanted due to dysfunction.

Material and Methods. We examined 17 leaflets from 6 BPHVs, dissected from the aortic and mitral positions during valve replacement. For microscopic analysis, fragments of the BPHV leaflets were frozen and serial sections were made using a cryotome. In order to study cellular infiltration and the degree of degenerative changes in the prosthetic biomaterial, the sections were stained with Gill’s hematoxylin and eosin; Oil Red O stain was used to assess lipid deposition. Immunohistochemistry was used for cell typing and detection of TIMP-1/-2. The stained samples were analyzed by light microscopy.

Results. Cellular and lipid infiltration of xenogeneic tissues was detected in all BPHV flaps studied. Recipient cells coexpressed pan-leukocyte and macrophage markers PTPRC/CD45 and CD68. Positive staining for TIMP-1/-2 co-localized with cell clusters but was absent in acellular sections.

Conclusion. Cells infiltrating xenogeneic BPHV tissues express TIMP-1/-2. This suggests that BPHV immune rejection pathophysiology is partially similar to that of calcific aortic stenosis.

Objective: to investigate the role of peroxiredoxin 6 (PRX6) in preserving the morphofunctional state of ischemic isolated kidney during perfusion.

Materials and methods. The model of an isolated perfused rat kidney was used. Ischemia time was 5 and 20 minutes, perfusion was 50 minutes. To evaluate the effectiveness of PRX6 at different ischemia times, we used the conventional criteria of kidney function and histological methods.

Results. During short warm ischemia times, exogenous PRX6 improves the morphofunctional state of an isolated kidney during perfusion. During this period, the main criteria for functioning of the isolated ischemic kidney reach acceptable values, renal parenchyma is without severe damage. By the end of perfusion, there was an increase in urine flow rate, glomerular filtration rate, fractional glucose reabsorption, urine urea concentration and proportion of primary urine from 1.5 to 2 times compared with the control lesion. At 20-minute ischemia, the isolated kidney can be recognized as non-viable according to the functioning criteria; the positive effect of PRX6 is leveled.

Conclusion. The use of recombinant peroxiredoxin 6 for preserving the morphofunctional state of isolated kidneys can be an effective approach in preventing ischemia–reperfusion injury.

Objective: to find evidence of the existence of distant lymphocytic RNA control of physiological myogenesis as a way to control the muscle tissue regeneration process.

Materials and methods. The study was conducted on male Wistar rats, n=33. In the first part of the experiment, 12 rats were subjected to regular 40-day physical activity (swimming), half of them were intraperitoneally injected 4 times with total RNA isolated from pig spleen lymphocytes at 30 days of age; 6 rats made up the intact control group. In histological preparations of different skeletal muscle groups, the width and cross-sectional area of muscle fibers, the area of nuclei, and the number of myocytes and myosatellite cells were evaluated. In the second part of the experiment, 15 intact rats were injected with the studied xenogeneic RNA and the amounts of ribonucleic acids in peripheral blood lymphocytes, spleen lymphocytes, and skeletal muscles were determined 2 hours and 24 hours after injection.

Results. After the 40- day physical activity, the width of the fibers and the area of myocyte nuclei in the skeletal muscles increased; the absolute number of myosatellite cells and the area of their nuclei did not change. After administration of xenogenic RNA in the trained rats, in addition to an increase in the thickness and cross-sectional area of muscle fibers, the absolute number of myosatellite cells in m. biceps femoris, in m. triceps brachii, and in m. pectoralis major increased 1.4-fold, 1.3-fold, and 1.4-fold, respectively; the area of myosatellite nuclei increased on average by 7%. In intact rats, two hours after xenogeneic RNA injection, the amount of RNA in skeletal muscles remained unchanged, it increased by 19% in spleen lymphocytes, and by 16% in peripheral blood lymphocytes. At 24 hours, the RNA amount in the lymphocytes remained significantly higher than the control values, while in the muscle tissue, it didn’t differ from the control.

Conclusion. Xenogeneic lymphocytic RNA stimulates physiological myogenesis by activating myosatellite cell proliferation.

Due to complications caused by the inevitable use of immunosuppressive drugs in organ and cell transplantation, the use of natural mechanisms of immunological tolerance identified in animal and human organisms arouses interest. It has long been known that there are certain areas in them, including the testis, where immune reactions are virtually impossible. Our review focuses on the role of Sertoli cells that provide testicular immune privilege. Methods of isolation and cultivation of Sertoli cells are described and their potentials in biology and medicine are discussed.

Objective: to obtain long-lived proliferating cells with progenitor features by dedifferentiation of mature rat hepatocytes using combinations of small molecules.

Materials and Methods. Hepatocytes isolated from rat liver by perfusion were cultured in the presence of a cocktail of three small molecules – Wnt signaling pathway activator (CHIR99021), TGF-β inhibitors (A83-01) and ROCK kinase (Y27632). The morphological characteristics and growth features of the culture were assessed using fluorescence and phase-contrast microscopy during cell culture. Cell proliferative activity was analyzed using real-time time-lapse imaging. The expression of surface and intracellular markers was analyzed using flow cytometry and high-resolution fluorescence microscopy.

Results. Using a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, long-lived proliferating cells that express progenitor cell markers, such as α-fetoprotein and HNF4α, were obtained from mature rat hepatocytes. The cells had hepatocyte-like morphology and formed discrete clusters of proliferating cells, forming a single cell layer during culturing. Removal of the small molecules from the medium led to expansion of fibroblast-like cells and elimination of potentially progenitor hepatocyte-like cells.

Conclusion. Proliferating progenitor cells can be obtained by dedifferentiation of mature hepatocytes.

In this review of current publications, we look at the molecular mechanisms of tolerance of the liver and its allografts in terms of minimization and possibilities of withdrawing immunosuppressive therapy, mainly in the long-term period after liver transplantation. Information about clinical trials with regulatory T cells (Tregs) for the purpose of tolerance induction is presented. Data from a new consensus study on individualization of immunosuppressive therapy regimens are presented. Options for possible withdrawal of immunosuppression both in the early and in the long term after liver transplantation (LT) are considered. We suggest a way to study the lymphoproliferative potential of a liver transplant recipient to be investigated, since not only rejection determines life expectancy, but also the degree of immunosuppression effect on bone marrow depending on patient age.

Transplantation in elderly patients is obviously more challenging due to existing underlying diseases, changes in pharmacokinetics of immunosuppressive drugs, polypragmasy, and transformation of immunoreactivity (immunosenescence). Our review presents data on modification of adaptive and innate immunity during aging. It also considers the possibility of both reduced and adapted immunosuppressive therapy in elderly renal transplant recipients in achieving an optimal balance between efficacy and complications.

Transforming growth factor beta 1 (TGF-β1) is an immunosuppressive and profibrogenic cytokine capable of influencing the development of graft rejection and graft fibrosis in solid organ recipients. The TGF-β gene has a significant polymorphism that may cause individual protein expression levels and be associated with post-organ transplant complications. It is believed that three TGFB1 polymorphic variants (rs1800469, rs1800470 and rs1800471) may be associated with the development of graft rejection, graft fibrosis and chronic dysfunction of a heart, liver or kidney transplant. A review of current literature presents the results of studies on the relationship between TGF-β1 gene polymorphisms and post-transplant complications in solid organ recipients. The findings of various studies of TGF-β1 gene polymorphism in solid organ recipients are not always unambiguous, and their results are often difficult to generalize even with the help of meta-analysis. Samples included in studies vary in terms of ethnicity, gender, age, and underlying medical conditions, while results are highly dependent on sample structure or latent relatedness. Currently available data suggest that TGFB1 polymorphism may determine a predisposition to the development of graft rejection, graft fibrosis and graft dysfunction in solid organ recipients, but this is not conclusive and requires further, larger studies.

Objective: to summarize current knowledge about the interactions between the lymphatic/cardiovascular systems and interstitial tissue, which are associated with heart failure (HF). The authors attempt to answer the fundamental question of whether lymphatic insufficiency is a cause or consequence of HF. Understanding lymph formation processes in HF will allow finding new ways of treating HF.

According to the International Agency for Research on Cancer, there were an estimated 19,292,789 new cancer cases in various localizations and 9,958,133 cancer deaths worldwide in 2020. These frightening figures clearly show that malignancies among the population is a pressing matter. The risk of post-transplant malignancy in solid organ recipients is 2–6-times higher than in the general population. Given the steadily increasing number of solid organ transplants worldwide and the gradual increase in life expectancy among organ recipients, studying the issues concerning risk factors and development mechanisms becomes a crucial task.