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Russian Journal of Transplantology and Artificial Organs

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Vol 22, No 1 (2020)
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https://doi.org/10.15825/1995-1191-2020-1

Editorial

Clinical Transplantology

8-15 903
Abstract
Objective: to determine the diagnostic value of galectin-3 in transplant recipients with myocardial fibrosis and acute heart transplant rejection, verified by endomyocardial biopsy. Materials and methods. The study included 124 patients with end-stage heart failure. Their ages ranged from 16 to 71 (average 48 ± 12) years, of which 106 (85%) were men and 18 (15%) were women. From 2013 to 2016, these patients underwent a heart transplant procedure at the Shumakov National Medical Research Center of Transplantology and Artificial Organs, Moscow, Russian Federation. Analysis of endomyocardial biopsy specimens was used to verify acute cellular, humoral rejection and myocardial fibrosis of the heart transplant. Severity and nature of fibrosis was evaluated using a qualitative imaging technique. Galectin-3 concentration was measured by enzyme immunoassay using Human Galectin-3 Platinum ELISA reagent kits (Bender MedSystems GmbH, Vienna, Austria). Results. In the long-term post-transplantation period, in comparison with the early post-transplantation period, the number of verified graft myocardial fibrosis increased by 88% in recipients who had acute rejection crises and by 37% in recipients who had no rejection crises. Graft myocardial fibrosis was detected more often in recipients who had acute humoral rejection than in those who had acute cell rejection (92% vs 75% of cases, respectively). Plasma galectin-3 levels in recipients with graft myocardial fibrosis was higher than in recipients without it (p = 0.05 1 year and p = 0.01 1–5 years after heart transplantation). In recipients who had acute rejection crises, the risk of developing graft myocardial fibrosis was 1.64 (RR = 1.64 ± 0.1 [95% CI 1.1–2.2]). Conclusion. Galectin-3 is a biomarker for myocardial fibrosis in acute heart transplant rejection.
16-25 828
Abstract
Isolated left ventricular noncompaction (LVNC) in adult patients is a rare form of primary cardiomyopathy. There have been several morphological studies of this condition in which a heart transplantation was performed. Objective: to analyze literature and clinical cases of patients with LVNC, macroscopic and histological data of the removed hearts. Materials and methods. At our center three patients (2 women aged 18 and 31, and 1 man aged 49) were morphologically diagnosed with LVNC had a heart transplant. We retrospectively analyzed the clinical, macroscopic and histological data of the removed hearts in these patients and the results of the transplants performed. Light microscopy of a fixed myocardial preparation stained with hematoxylin and eosin was used for histological examination. Results. A histological examination confirmed the presence of LVMI in these patients. Conclusion. LVMI is a rare disease, that can occur asymptomatic or cause severe congestive heart failure, requiring transplantation.
26-34 948
Abstract
Objective: to conduct comparative analysis of the expression levels of microRNA-101, microRNA-142, microRNA- 27, microRNA-339 and microRNA-424 in patients with severe chronic heart failure and in heart recipients in the early and long-term period following heart transplantation and to determine the association with acute transplant rejection. Materials and methods. The study included 46 heart recipients, among whom were 36 men (78.3%); the average age of the recipients was 47.7 ± 10.8 (16 to 67) years, and 12 patients with end-stage chronic heart failure, among whom were 8 men (66.7%); the average age of the patients was 46.1 ± 6.4 (37 to 64) years. The control group consisted of 12 healthy individuals, not significantly different by gender and age. microRNA expression levels in blood plasma were determined through quantitative polymerase chain reaction (Q-PCR). Transplant rejection was verified via morphological analysis of endomyocardial biopsy specimens. Results. Blood plasma of patients with end-stage chronic heart failure had significantly higher expression rates of microRNA-101, microRNA-27, microRNA-339 and microRNA-424 than in healthy individuals (p < 0.02). In the early stages following transplantation, the expression levels of microRNA-101 and microRNA-27 in heart recipients were significantly lower than in patients with severe chronic heart failure (p < 0.003). A year or more after transplantation, there were no significant differences in the expression levels of microRNA-101, microRNA- 142, and microRNA-339 in heart recipients and in healthy individuals. In recipients with acute rejection, the expression levels of microRNA-101 and microRNA-27 significantly differed from that of recipients without signs of rejection (p = 0.04 and p = 0.03, respectively). Conclusion. The obtained data on changes in the expression levels of microRNA-101 and microRNA-27 in heart recipients with acute transplant rejection suggests possible diagnostic value of these biomarkers in determining the risk of rejection.
35-39 1290
Abstract
Objective. While international guidelines necessitate Voiding Cystourethrogram (VCUG) for pediatric patients, it is unnecessary for the evaluation of adult patients without urological disorders as renal transplant candidates. The objective of this study was to evaluate the results of adult candidates who underwent VCUG before transplantation and to demonstrate the necessity for this imaging. Methods. A retrospective study of the data of 1265 adult candidates who underwent VCUG before transplantation at our center, was undertaken. VUR, the presence of Postvoiding residual urine (PVR) (>100 ml), Low bladder capacity (LBC) (<100 ml), and urethral pathologies were evaluated with VCUG. Results. The mean age was 42.3 ± 1.3. The mean dialysis period was 27.8 ± 4.2 months. According to the VCUG results, 19.2% of the patients had pathological findings. On the other hand, the rate of urological disorders was only 5.1%, according to end-stage renal disease (ESRD) etiologies. VCUG outcomes indicated bilateral high-grade reflux in native kidneys in 4.4% (n = 56) of the candidates, unilateral high-grade reflux in 4.1% (n = 52), bilateral low grade reflux in 2.1% (n = 26), unilateral low-grade reflux in 2.4% (n = 30), and reflux in rejected transplanted kidney in 2.3% (n = 29). In addition, significant LBC was noted in 4.8% (n = 61), significant PVR in 1.1% (n = 14), and urethral stricture in 0.5% (n = 6) of the candidates. Conclusion. VCUG should be considered as a part of routine evaluation in adult renal transplant recipient candidates as well as in pediatric candidates, even if their ESRD etiologies are not due to urological disorders.
40-49 995
Abstract
Objective: to analyze the features of the pattern of lymphocyte subpopulations and the functional activity of peripheral blood mononuclear cells in older adult patients with chronic kidney disease. Materials and methods. The study featured 21 patients with chronic kidney disease (CKD), over 55 years of age, who underwent kidney transplantation (KT) from unrelated suboptimal donors. The average age was 61.4 ± 4.5 years (55 to 69). Comorbidity was assessed using the CIRS-G scale; the average number of points was 13.6 ± 5.09. The control group consisted of 21 volunteers, aged 55–70, without acute inflammatory diseases and signs of chronic kidney disease (CKD). The average age was 61.1 ± 4.4 years, the average CIRS-G score was 12.11 ± 6.04. In all patients, the pattern of lymphocyte subpopulations of peripheral blood was evaluated by flow cytometry. Vital computer laser cytomorphometry was used to assess the functional state of peripheral blood mononuclear cells. The Functional Activities Index (FAI) was evaluated to indirectly assess the degree of functional activity of cells. Results. In CKD patients before KT, there was a decrease in the proportion of CD4 cells (p = 0.009), an increase in the proportion of CD8 cells (p = 0.02), a decrease in the CD4/CD8 ratio (p = 0.017), an increase in the proportion of natural killers (p = 0.025) compared with healthy volunteers. Moreover, a decrease in the total proportion of CD3 cells, an increase in HLA-DR expression on CD3 cells, and an increase in the proportion of B cells were statistically insignificant: p = 0.137, p = 0.072 and p = 0.135, respectively. On the fifth day after KT, the proportion of CD3 cells increased (p = 0.017) mainly due to an increase in the proportion of CD4 cells (p = 0.002) compared to the pre- KT index. The proportion of natural killers (p = 0.002) and HLA-DR expression on CD3 cells (p < 0.0001) also increased. An increase in the proportion of CD8 cells and in the CD4/CD8 ratio, and a decrease in the proportion of B cells were statistically insignificant: p = 0.439, p = 0.277, and p = 0.236, respectively. A decrease in FAI was noted in patients with CKD before KT in comparison with healthy volunteers (p = 0.0138). After ATP, this indicator significantly increased compared to the pre-KT value (p < 0.0001) and exceeded the FAI value in healthy volunteers (p < 0.0001). In healthy volunteers, there was no significant correlation between the functional activity of peripheral blood mononuclear cells and age (r = –0.263 [95% CI –0.6236; 0.1907], p = 0.264, r2 = 0.069). At the same time, significant negative correlation between FAI and age was noted in CKD patients: r = –0.52 [95% CI –0.7771; –0.1135], p = 0.0157, r2 = 0.27 before KT; r = –0.418 [95% CI –0.7559; –0.06256], p = 0.0272, r2 = 0.175 after KT. Conclusion. Older adult CKD patients before and after KT were likely to have significant changes in the morphofunctional state of peripheral blood mononuclear cells and pattern of lymphocyte subpopulations. Moreover, the severity of changes in the functional state of these cells had a strong correlation with age, which was not observed in the group of healthy volunteers. This should be considered when choosing immunosuppressive therapy in older kidney transplant recipients.
50-54 887
Abstract
Objective: to analyze negative laboratory results of cadaver cornea donor screening during preparation of corneas for transplantation according to data from the internal registry of donors of the eye bank (EB) of the Fyodorov Eye Microsurgery Federal State Institution and the European Eye Bank Association (EEBA) from 2011 through 2015. Materials and methods. Data analysis was carried out using the internal registry of EB donors and the EEBA annual directories. The analyzed data included the number of eyeballs obtained, the frequency of incomplete tests (hemolysis for EB) and positive serological results for human immunodeficiency virus (HIV-1 and HIV-2), viral hepatitis B, viral hepatitis C and syphilis. Results. In just 5 years, the EB received 3,479 eyeballs. After hemolysis of donor blood samples, 13.9% (n = 486) of corneas were excluded from the EB. EEBA recorded fewer inconclusive tests during the same period. After hemolysis and positive serological tests, 19.4% (n = 676) of corneas were excluded from the EB. Overall, the number of positive serological tests in EBs was far higher than in the EEBA data. Frequency of positive HIV tests (HIV-1 and HIV-2) and syphilis in EB showed low variability annually, while incidence of hepatitis B increased in 2015. For the analyzed period, positive serology for hepatitis C was found to be prevalent among EB donors. Mixed infections were quite often recorded in blood samples. Conclusion. Based on analysis conducted, positive serology and hemolysis were the main contraindications and led to exclusion of 33.3% (n = 1162) of cadaver donor corneas received in EB. Frequency of positive serological tests for indicated infections in EB was higher than in the EEBA data, with significant predomination of hepatitis C.
55-58 1367
Abstract
Objective: to evaluate the first results of the Botkin Hospital transplant program. Materials and methods. From June 2018 to October 2019, 100 solid organ transplants were performed at the Botkin City Clinical Hospital. Out of the 100 transplantations, 72 were kidney transplants (average age of recipients was 45.65 ± 11.35 years, HLA match averaged 2.09 ± 1.03) and 28 were liver transplants (average age of recipients was 50.14 ± 7.62 years, average MELD was 17.78 ± 3.28 (14–34). Results. After transplantation, there was no 30-day mortality. Postoperative complications following kidney transplantation were established in 11 patients (15.2%). In 3 patients (4.3%) – suppuration of postoperative wound, in 2 patients (2.8%) – hematomas in the area of the postoperative suture during hemodialysis, in 5 patients (6.9%) – retroperitoneal lymphocele, in 1 patient (1.4%) – urosepsis. There were 4 cases (5.5%) of acute rejection, 3 cases (4.2%) of humoral rejection, and 1 case (1.3%) of cellular rejection. Early postoperative complications following liver transplantation were detected in 2 patients (7.2%). In one patient – hematoma under the right lobe of the liver on the 1st day after surgery, the diaphragm was the source of bleeding, in one patient – ascites leakage through postoperative sutures, which required relaparotomy. In 2 patients (7.2%), postoperative complications were found in the separated postoperative period. In one case, of choledochocholedochal anastomotic stricture – stricture stenting was performed with coated nitinol stent. In another case, acute adhesive intestinal obstruction, which required laparotomy, adhesiolysis. Conclusion. Implementation of the transplantation program in multidisciplinary hospitals can boost transplant care in a district and improve the treatment results of patients with terminal organ damage.

Heart Transplantation and Assisted Circulation

59-71 1623
Abstract
Objective: to conduct comprehensive comparative analysis of the patency rate of native arteriovenous fistula (AVF) for central vein stenosis (CVS) after endovascular balloon angioplasty and palliative surgery. Materials and methods. The retrospective study included 80 patients with confirmed central vein stenosis: subclavian, brachiocephalic veins, inferior vena cava, or multiple lesions. The experimental group included 39 patients who underwent percutaneous balloon angioplasty. The control group included 41 patients who, for various reasons, did not do balloon angioplasty, but underwent palliative interventions: thrombectomy, proximalization of arteriovenous anastomosis, AVF blood flow-reducing surgical procedures. Results. Primary patency (time interval between the first intervention for CVS and the second intervention) in the experimental group was 61.5% [95% CI 44.5; 74.7] and 15.4% [95% CI 6.2; 28.3] at 6 and 12 months, respectively. In the control group, it was 39% [95% CI 24.3; 53.4] and 0% respectively. Hazard ratio (HR) 0.5337 [95% CI 0.3381; 0.8427], log-rank test p = 0.0011. No differences in functional primary patency (time interval between the start of using AVF and the first intervention for CVS) were found: 89.7% [95% CI 74.9; 96] and 30.8% [95% CI 17.3; 45.4] at 1 year and 3 years, respectively, in the experimental group, and 80.5% [95% CI 64.8; 89.7] and 24.4% [95% CI 12.7; 38.2] in the control group. There were no differences between the groups HR 0.7695 [95% CI 0.4952; 1.196], log-rank p = 0.2259. In the experimental group, strong negative correlation between primary patency and functional primary patency was detected: r = –0.627 [95% CI –0.787; –0.388], p < 0.0001. In the control group, no such correlation was found: r = 0.049 [95% CI –0.262; –0.351], p = 0.7599. Thus, the later CVS developed, the less effective balloon angioplasty was. Balloon angioplasty significantly increased duration of AVF use after first intervention for CVS (secondary patency): 84.6% [95% CI 68.9; 92.8], 66.7% [95% CI 49.6; 79.1] and 17.9% [95% CI 7.9; 31.3] at 6, 12 and 24 months, respectively in the experimental group. In the control group, it was 56.1% [95% CI 39.7; 69.6], 19.5% [95% CI 9.2; 32.7] and 0%. HR 0.4009 [95% CI 0.2481; 0.6477], log-rank p < 0.0001. Functional secondary patency (total duration of AVF use) was: 100%, 74.4% [95% CI 57.6; 85.3] and 12.8% [95% CI 4.7; 25.2] at 1, 3 and 5 years in the experimental group, and 95.1% [95% CI 81.9; 98.8], 36.6% [95% CI 22.3; 51] and 4.9% [95% CI 0.9; 14.5] in the control group. HR 0.5661 [95% CI 0.3598; 0.8906], log-rank p = 0.0067. Conclusions. 1. Central vein stenosis inevitably cuts vascular access from the ipsilateral side. 2. Balloon angioplasty allows to slightly prolong AVF use but it cannot radically change the long-term results of CVS treatment. 3. The outcome of balloon angioplasty greatly depends on the length of the period from the time the use of AVF started to the time CVS developed. 4. Multiple repeated balloon angioplasties are apparently justified in patients for whom creating a new vascular access might not be possible. 4. AVF volumetric blood flow velocity is an important factor determining the severity of CVS clinical manifestations and whether repeated surgical interventions are needed.
72-78 840
Abstract
Objective: to investigate dependence of the mechanical properties of mitral annuloplasty rings on heat annealing modes. Materials and methods. The study evaluates the nature of change in stress–strain curves under uniaxial compression of experimental samples processed at varying annealing temperature, duration and pressure. Results. It was noted that higher exposure, temperature, and lower pressure led to increased structural rigidity and strength for small strains. Moreover, the extent of influence of annealing temperature and duration was comparable. A 40% (500–700 °C) change in temperature altered the mechanical properties of the ring – 20% increase in strength. A similar change in heat treatment time (4.5–6.5 min) resulted in a 27% increase in the force required for a 15% compression. Conclusion. The experimental dependences presented in the work allow recommending main parameters for heat treatment mode: temperature range 600–700 °C, 10.5 minutes exposure time, and 0.1–0.5 atm air pressure in the furnace chamber.
79-85 930
Abstract
A prosthesis-patient mismatch (PPM) describes a state in which the valve prosthesis implanted during surgery is too small in relation to the patient’s body size. This leads to high transvalvular pressure gradients. We investigate direct results and dependence of transvalvular pressure gradients on body mass index and surface area in patients after correction of aortic valve defects using small-diameter BioLAB prosthesis. Material and methods. From January 2011 to August 2018, 65 small-diameter (18, 20) BioLAB scaffold xenopericardial prostheses were implanted in aortic position at the Department of Emergency Surgery for Acquired Heart Defects, Bakulev National Medical Research Center of Cardiovascular Surgery. The average age of the patients was 75.4 ± 4.1 (65–86 years). The average patient body mass index was 25.74 ± 5.11 kg/m2 (19.57–39.54). The average body surface area was 1.79 ± 0.15 (1.54–2.18). Results. Isolated aortic valve replacement was performed in 38 (58%) patients, the rest of the surgeries were combined with other techniques. There were no reoperations due to early prosthetic endocarditis or prosthetic dysfunction in hospital. Hospital mortality was 6% (4 patients). Correlation dependence of peak pressure prosthesis gradient on body surface area and body mass index was 10% and 8%, respectively. Conclusions. This study confirmed the safety and effectiveness of using small-diameter BioLAB scaffold xenopericardial prostheses in aortic valve position.
86-96 1163
Abstract
The need for small-diameter grafts for replacing the damaged area of the blood pool is still very high. These grafts are very popular for coronary artery bypass grafting. Polymeric synthetic grafts are an alternative to autografts. A promising area of tissue engineering is the creation of a biodegradable graft. It can serve as the basis for de novo generation of vascular tissue directly in the patient’s body. Optimization of the polymer composition of products has led to improved physicomechanical and biocompatible properties of the products. However, the improvements are still far from needed. One of the decisive factors in the reliability of a small-diameter vascular graft is the early formation of endothelial lining on its inner surface, which can provide atrombogenic effect and full lumen of the future newly formed vessel. To achieve this goal, grafts are modified by incorporating bioactive molecules or functionally active peptide sequences into the polymer composition or immobilizing on its inner surface. Peptide sequences include cell adhesion site – arginine-glycine-aspartic acid (RGD peptide). This sequence is present in most extracellular matrix proteins and has a tropism for integrin receptors of endothelial cells. Many studies have shown that imitation of the functional activity of the natural extracellular matrix can promote spontaneous endothelization of the inner surface of a vascular graft. Moreover, configuration of the RGD peptide determines the survival and differentiation of endothelial cells. The linker through which the peptide is crosslinked to the polymer surface determines the bioavailability of the RGD peptide for endothelial cells.

CLINICAL REPORTS

97-106 858
Abstract
The paper presents the world’s first clinical case of two full-term successive pregnancies in a patient following simultaneous liver-kidney transplantation with reno-portal transposition. Both pregnancies ended with the birth of healthy children and favorable course of postpartum and long-term periods. The features of management and childbirth are highlighted. Literature review on this problem is presented.
107-113 1497
Abstract
We present a case of simultaneous laparoscopic bilateral nephroureterectomy, cadaveric kidney allotransplantation and performance of vesicostomy. This observation shows that patients with end-stage kidney disease, primarily caused by neurogenic bladder dysfunction, can be successfully treated via surgery. The course of early postoperative period and further rehabilitation did not differ significantly from that obtainable after standard kidney allotransplantation.
114-117 1010
Abstract
Various research has shown that non-melanocytic malignant skin lesion is one of the most common post-kidney transplant neoplasms. Multiple lesions and a more aggressive clinical course are more common in kidney transplant patients than in the general population. This paper presents a case of malignant skin neoplasms in a patient 10 years after cadaveric kidney transplantation. The patient received standard 3-component immunosuppression with satisfactory graft function (serum creatinine level remained at 157–178 μmol/L). Scalp neoplasm was removed. Histological examination revealed a morphological picture characteristic of basal cell carcinoma with squamous differentiation. Subsequently, a relapse of the skin neoplasm of the temporal region, as well as new lesions in the frontal region and the skin of the anterior chest wall, were discovered. Despite surgical treatment and close-focus x-ray radiation, the disease rapidly progressed and eventually led to death. Squamous cell carcinoma can progress very rapidly in patients after solid organ transplantation, despite ongoing combination treatment. Perhaps in such cases, it is worth cancelling immunosuppressive therapy completely and removing the kidney graft in order to control progression of the malignant tumor process.
118-122 886
Abstract
Chronic heart failure is one of the most dreadful complications in the early postoperative period following lung transplantation. At the same time, the effect of using levosimendan in the early post-lung transplant period is currently insignificant and remains debatable. This paper presents a clinical case where levosimendan was successfully used in a patient with right ventricular heart failure during lung transplantation undergoing central venoarterial extracorporeal membrane oxygenation (VA-ECMO).

REGENERATIVE MEDICINE AND CELL TECHNOLOGIES

123-133 1202
Abstract
One of the pressing issues in tissue engineering is on how to obtain an artificial matrix that can simulate a biological microenvironment for cells. When creating a bioengineered pancreatic construct, a tissue-specific scaffold obtained from decellularized pancreatic tissue can serve as such matrix. Objective: to obtain and study the characteristic properties of a tissue-specific pancreas scaffold from decellularized human pancreatic fragments. Materials and methods. The decellularization protocol included 3 freeze/thaw cycles, followed by treatment with surfactants (sodium dodecyl sulfate and Triton X100). At each decellularization stage, samples were routinely stained with hematoxylin and eosin and for total collagen. In addition, immunohistochemical staining of decellularized human pancreas (DHP) for type I collagen and elastic fibers was performed. Cell nuclei in the original samples and the resulting matrix were visualized using DAPI fluorescent staining. DNA quantity in the native and decellularized pancreatic tissue was determined. The cytotoxicity of the tissue-specific matrix was evaluated in vitro by direct contact. The matrix properties of DHP samples were determined using mesenchymal stem cells (MSCs) of human adipose tissue. Results. A pancreatic decellularization method is proposed. This method allows to obtain a tissue-specific matrix in the form of a connective tissue scaffold completely free of detritus with preserved thin-fiber mesh-like structure, in which elastic and collagen fibers, including type I collagen, are identified. DAPI staining confirmed the absence of nuclear material in the decellularized matrix, while residual amount of DNA did not exceed 0.1%. Absence of matrix cytotoxicity and its ability to maintain adhesion and proliferation of human adipose tissue-derived MSCs was proved. Conclusion. As one of the stages in creating a bioengineered pancreatic construct, a method has been developed for producing a biocompatible (lack of cytotoxicity and immunogenicity) tissue-specific scaffold from decellularized human pancreatic tissue. In the scaffold, the morphofunctional properties of the native extracellular matrix-based scaffolds of the pancreas are preserved. Adhesion and proliferation of cell cultures are ensured.
134-141 767
Abstract
Objective: to study the effect of intrasplenic implantation of a tissue-engineered pancreatic construct (TEPC) on experimental diabetes mellitus. Materials and methods. Floating islet-like cultures (FICs) were obtained from the pancreas of newborn rabbits. To form TEPC, FICs were incubated with biopolymer microheterogeneous collagen-containing hydrogel (BMCH). TEPC samples were injected into the splenic pulp of rats with streptozotocin-induced diabetes. Results. TEPC with insulin-producing activity was formed on the 7–10th day of incubation of FICs with BMCH. After TEPC implantation in recipient rats, persistent decrease in hyperglycemia and disappearance of clinical signs of diabetes were noted. Histological analysis revealed the presence of groups of islet cells without signs of immune cell response at the TEPC implantation site. Conclusion. Our findings indicate that xenogeneic islet cells that were part of the TEPC of the pancreas can survive and actively function after implantation in the splenic pulp of diabetic rat.
142-156 984
Abstract

Objective: to develop a model of a biomedical cell product that is consistent with the «homologous drug» strategy  based on protocols for preparing the cell component and scaffold carrier for preclinical studies on a large laboratory  animal (pig). Materials and methods. Biomedical cell products and skin equivalents (SE), were formed using  plasma cryoprecipitate prepared from blood plasma of healthy donors and mesenchymal stem cells (MSCs) of  human adipose tissue. Cryoprecipitate from pig blood plasma and human adipose tissue-derived MSCs were used   to form model skin equivalents (mSE). Bright-field microscopy, phase-contrast microscopy (Leica DMI 3000B)  and fluorescence microscopy (Cytation 5 imager; BioTek, USA) were used to monitor the state of cells in the  culture and in the composition of the equivalents. Scaffolds for equivalents were tested for cytotoxicity (MTT test,  direct contact method). The cell distribution density was characterized by author’s method (Patent No. 2675376  of the Russian Federation). Results. An mSE was developed for preclinical studies on a large laboratory animal  (pig). In the mSE, components that change from halogen to xenogenic conditions during transplantation to the  animal were replaced. A comprehensive approach to preparing mSE was presented. It includes sampling of primary  pig biomaterial, extraction and characterization of adipose tissue-derived MSCs, preparation of a scaffold  carrier for the corresponding «homologous drug» strategy. Cytotoxicity of the mSE scaffold was evaluated. It  was shown that mSE provides mechanical support (similar to SE) to cells, as well as comparable development of  cellular events during cultivation. Conclusion. A model of a biomedical cell product was developed. This model  is consistent with the «homologous drug» strategy for preclinical studies on a large laboratory animal (pig). The  paper presented a comprehensive approach to developing a model equivalent based on protocols for preparation  and testing of the cellular component, the scaffold carrier and the ready-to-use model equivalent.

157-164 1048
Abstract

Objective: to study the morphological features of formation of the eyeball orbital stump using a titanium nickelide  tissue-engineered construct and a suspension of autologous blood mononuclear leukocytes in vivo. Materials  and methods. Experiments were performed on 54 sexually mature Wistar rats weighing 200–250 g. The animals   were divided into 3 groups, depending on type of surgical intervention: group 1 (n = 18) consisted of animals in  which eyeball orbital stump was formed after evisceroenucleation through implantation of a titanium nickelide  tissue-engineered construct and a suspension of autologous blood mononuclear leukocytes in the scleral sac; group  2 (n = 18) – the eyeball orbital stump was formed through implantation of titanium nickelide tissue-engineered  construct in the scleral sac; group 3 (n = 18) – orbital stump was formed using an Alloplant implant. Results.  It was established that in group 1 rats, on day 7 following surgery, the specific volume of connective tissue was  7.9 times (рU = 0.048) higher than in group 2 rats and 15.8 times (рU = 0.039) higher than in group 3 rats. On  day 14 after surgery, the volume of connective tissue in the eyeball orbital stump of group 1 rats reached the highest  value compared to that in the other groups. The numerical density of newly formed vessels in the eyeball orbital  stump of group 1 rats, starting from day 14 after surgery up to the end of experiment (day 21), was statistically  significantly higher than that in the other groups. Moreover, on day 21, this indicator was 4.0 times (рU = 0.001)  higher in group 1 rats than in group 2 rats and 9.8 times (рU = 0,0003) higher than in group 3 rats. Conclusion.  Implantation of titanium nickelide tissue-engineered construct and a suspension of autologous blood mononuclear  leukocytes into the scleral sac after evisceroenucleation in an in vivo experiment leads to accelerated maturation  of the connective tissue and intensive vascularization in the eyeball orbital stump. This ensures strong fixation of  the implant and reduces risk of rejection.

165-173 1021
Abstract
Chronic ulcers are a common and socially significant problem worldwide. Autodermoplasty is the gold standard treatment for chronic ulcers. However, it is not always possible to perform this surgical procedure for a rather large group of patients, due to some reasons, which include high risk of autodermotransplant rejection, lack of donor material, and patient’s unwillingness to undergo surgery with an often unpredictable result. A potential solution to the problem is to use skin equivalents from allogeneic donor material. The use of allogeneic (donor) human cells makes it possible to fill the deficit of the patient’s donor resources and close wound without causing additional injury to the patient. This paper provides an overview of the application of foreign and domestic biomedical cell products in clinical trials and real clinical practice. We draw conclusions on the efficiency of the considered biomedical cell products in the treatment of chronic ulcers, evaluate the conducted research, and make recommendations on the most efficient use of allogeneic dermatotropic biomedical cell products.

LITERATURE REVIEWS

174-183 2441
Abstract
From the standpoint of socio-humanitarian knowledge, the paper analyzes the problem of global organ shortage. The basic ideas of the international medical community about organ shortage and the main proposals for overcoming it are considered. Special emphasis is placed on the three most revealing national self-sufficiency strategies adopted by donor agencies – American, Spanish and Iranian strategies. The issue of influence of cultural differences and socio-economic inequality on established organ donation practices is discussed using Mexico, Turkey, Pakistan and Bangladesh as examples.
184-195 1188
Abstract
The review includes results of retrospective and prospective clinical studies (foreign and national) and guidelines on the use of transplantation technologies for treatment of type 1 diabetes and pancreatogenic diabetes in chronic pancreatitis and pancreatic conditions. Modern data on prevalence of diabetes and modern insulin delivery methods are presented. Results of transplantation of pancreas and islets of Langerhans in primary insulin-dependent conditions are considered. Analysis of the technology for isolation and autotransplantation of islets after pancreatectomy in chronic pancreatitis and benign tumor diseases are given.
196-208 2894
Abstract
This review looks at the use of fibrin in vascular tissue engineering (VTE). Autologous fibrin is one of the most affordable biopolymers because it can be obtained from peripheral blood by simple techniques. A description and comparative analysis of the methods and approaches for producing fibrin gel is provided. The ability of fibrin to promote cell attachment and migration, survival and angiogenesis, to accumulate growth factors and release them in a controlled manner, are unique and extremely useful in VTE. Fibrin gels can serve as a three-dimensional matrix molded in different sizes and shapes to be applied in a variety of ways, including as a scaffold, coating, or impregnation material. Fibrin’s high porosity and biodegradability allows controllable release of growth factors, yet fibrinolysis must be tightly regulated to avoid side effects. We discuss the main methods of regulating the rate of fibrinolysis, as well as possible side effects of such exposure. Low mechanical strength is the main limitation in using fibrin as a scaffold for vascular tissue engineering. Possible options for increasing the strength properties of fibrin matrix and evaluating their effectiveness are presented. We propose that unique biocompatibility and ideal biodegradation profile of fibrin justify its use as a scaffold material for developing an ideal fully autologous small-diameter tissue-engineered vascular graft.
209-219 1127
Abstract
The decision to choose a particular patient for kidney transplantation is made through two consecutive decisions: decision to include the patient on the waiting list and decision to select a patient competitively among several candidates for transplant. Both decisions are taken amidst many competing priorities and require a multidisciplinary approach. This paper provides comparative analysis of the principles of maintaining a waitlist and selecting a donor–recipient pair in Russia, Europe (Eurotransplant) and the USA (UNOS). Donor–recipient pair is selected based on the traditional hierarchical scheme of decision rules. Unlike Eurotransplant and UNOS, there are no uniform standards in Russia for assessing the quality of a donor organ. The widespread and largely vague «old for old» principle should be harmoniously fitted into the general outline of donor kidney distribution. The second difference in the national distribution system of donor kidneys is the choice in favor of a candidate with a lesser degree of sensitization. With high frequency of positive cross-test, this principle, in a synergistic manner, greatly reduces the availability of transplantation for highly sensitized candidates. The quality of donor organ and unconditional priority on highly sensitized candidates are the conceptual fundamental principles of organ distribution in the US and Europe. Under donor kidney shortage, selecting a recipient is always competitive. The choice of a candidate can be based on a patient-oriented approach (a choice in favor of the candidate whose transplantation will most likely reduce the risk of death; for example, an «emergency» waiting list) or an alternative – a utilitarian approach (choosing the candidate with the longest predictable life expectancy). However, radical commitment to one of these approaches inevitably reduces availability of kidney transplantation for a specific category of patients. For a justified choice of recipient, it is necessary to correlate such factors as comorbidity, waiting time, age, histocompatibility and quality of donor kidney. This would achieve a shaky balance between utilitarian approach and patient-oriented approach. The principles of creating a waiting list and a system for efficient distribution of donor organs practiced by foreign organizations cannot be simply copied and reproduced in Russia. It is necessary to adapt and validate such principles for the local patient population. The objective difficulties of such an analysis dictate the need to address it on a national scale. This would ensure equitable distribution of donor organs to all patients in need and obtain the best transplant results. Moreover, this would make it possible to achieve the full potential of donor organs. Conclusions. The situation in transplantological and nephrological care in Russia is gradually changing. This determines the need to adapt and standardize approaches to allocation of cadaveric donor kidneys in order to ensure equal access to transplantation for different patients and fullest realization of their potential. Removing organ distribution from the area of responsibility of local coordination councils, introducing a unified policy for distribution of donor organs and choosing a specific recipient will reduce the subjectivity of decisions and, possibly, improve transplantation results.

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ISSN 1995-1191 (Print)