Clinical Transplantology
Review of the main research areas and the most significant results obtained in recent years in the Federal Research Center of Transplantology and Artificial Organs including heart transplantation, lung transplantation, the evolution of liver transplantation and kidney transplantation is presented. The article also describes advanced developments in the field of creating artificial organs – artificial circulatory support systems – and regenerative medicine, nano- and cellular technologies, the creation of bioartificial organs.
Aim. The study was aimed to assess the prevalence and risk factors of hypertension in cardiac recipients.
Materials and methods. End-stage heart failure patients who received cardiac transplant between 01.01.2013 and 31.12.2016 in V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs (Moscow) and survived 3 months after surgery were included and followed up for 999.4 ± 774.3 (108–1587) days. Young patients (<18 y/o) and patients after repeated (n = 18) or multi-organ transplantation (n = 3) were excluded.
Results. 353 cardiac recipients aged 45.6 ± 1.6 years (18.1% females and 81.9% males) were enrolled into the study. Hypertension was prevalent in 17.6, 42.8, 62.3 and 71.4%, respectively, before, in 3 months, in 1 year, and 3+ years after the transplantation. The study revealed significant relationship between post-transplant hypertension incidence and pre-op body mass index (р = 0.026), serum creatinine (р < 0.001), preexisting hypertension (RR = 1.36, р = 0.022) and renal failure, as well as donor heart posterior wall thickness (р = 0.034), post-transplant dialysis (RR = 1.85, р < 0.001), and antibody mediated rejection episodes (RR = 1.7, р = 0.001). Uncontrolled hypertension in cardiac recipients was related to poor compliance and new-onset post-transplant renal failure.
Conclusion. Hypertension is highly prevalent among our population of cardiac recipients. The combination of various etiologic mechanisms, multiplex therapy and subjective factors calls for the careful individual patient management.
Heart Transplantation and Assisted Circulation
Aim. To study the specific activity of the microemulsion form of the matrix insulin transdermal delivery system in vivo on the experimental streptozotocin model of type I diabetes.
Materials and methods. Male rats (n = 25) were randomized to the experimental and control groups. TDS insulin with a microemulsion composition was applicated to the animals of the experimental group (n = 15) for 4 days with daily replacement of TDS and control of the glycemia level. The glycemia level of the control group rats (n = 10) was determined throughout the experiment. The blood glucose concentration was measured using glucometer One Touch Select (USA).
Results. The average blood glucose level in experimental group was 28.4 ± 2.3 mmol/l before application of TDS insulin. The average glycemic index was 21.2 ± 3.1 mmol/l (p < 0.001) during of TDS application. The blood glucose decrease was 26 ± 8% relative to baseline values. The glycemia was 28.4 ± 1.4 mmol/l in the control group rats throughout the experiment.
Conclusion. A significant decrease of blood glucose level with TDS insulin application in rats with experimental type 1 diabetes demonstrates the existence of the specific activity of the microemulsion matrix transdermal delivery system of insulin.
Aim. The article presents the results of wearable artificial kidney (WAK) biomedical trial based on peritoneal dialysis with continuous dialysate regeneration.
Materials and methods. The trial was carried out on a 15-kg dog. First stage: dialysis was carried out on healthy dog to evaluate effect of WAK on blood biochemical indicators. Second stage: 200 ml of X-ray contrast agent was injected into dog’s bloodstream to simulate acute kidney failure.
Results. During trial (39.5 hours) WAK was performing continuous peritoneal dialysis with dialysis fluid regeneration. During second stage (34 hours) creatinine and uric acid were eliminated from dialysis solution at the rate of 0.3 mg/h, urea was eliminated at the rate of 0.15 g/h, total removed ultrafiltrate volume was 350 ml. At the end of the second stage blood biochemical indicators stabilised in the range of normal values.
Conclusion. Developed WAK can perform continuous blood purification and ultrafiltration with no pathologic impact on blood biochemical indicators.
Regenerative Medicine and Cell Technologies
In situ crosslinkable hydrogels have been widely used as therapeutic implants and vehicles for a broad range of biomedical applications including tissue regenerative medicine because of their biocompatibility and easiness of encapsulation of cells or signaling molecules during hydrogel formation. Recently, these hydrogel materials have been widely utilized as an artificial extracellular matrix (aECM) because of its structural similarity with the native extracellular matrix (ECM) of the human body and its multi-tunable properties. Various synthetic, natural, and semisynthetic hydrogels have been developed as engineered cellular microenvironments by using various crosslinking strategies. In this review, we discuss how in situ forming hydrogels are being created with tunable physical, chemical, and biological properties. In particular, we focus on emerging techniques to apply advanced hydrogel materials for engineered cellular microenvironments.
A rapidly growing development of tissue engineering promotes the increasing interest in the obtainment of various decellularizedtissues and organs. Minimal quality evaluation criteria of obtained tissue engineered constructions have been previously specified. In the discussionpaper the group of authors considers the morphological methods of matrix evaluation applied by various researchers on the model of heart decellularization. The analysis of modern literature and the authors’ own researches have shown that morphological evaluation of decellularization quality has to be complex and should consist of several stages which include both basic and additional evaluation methods.
Literature Reviews
Diabetes mellitus is a significant social problem. In the Russian Federation, the prevalence of diabetes type 1 is 340.000 people, 21% of them having diabetic nephropathy, as well as other secondary complications leading to disability and high mortality. There are several options for diabetic patients with chronic kidney disease dialysis: kidney transplantation with insulin therapy, simultaneous kidney-pancreas transplant or islet transplant. Good long-term results could be obtained by the whole pancreas and kidney combined transplantation through maximum metabolism recovery comparing to other replacement therapy options. The recipientselection with special attention to the cardiovascular system evaluation is essential to successful transplantation. The proper pancreatic graft assessment needs a wide range of criteria to be analyzed. Integral scores can simplify and systematize the assessment. The choice of preservation technique is important to pancreatic graft ischemia-reperfusion injury minimization. Despite the progress in graft preservation methods, cold storage using University of Wisconsin (UW) solution remains to be the gold standard. The evolution of surgical technique has resulted in utilizing the most physiologic variations of exocrine drainage and venous outflow of the pancreas, so-called portoenteric drainages, which were designed to improve remote metabolic effects and to reduce complications probability.
Formation of tissue-engineered construct was performed in a specially developed bioreactor. At first, a cellengineered construct of human cartilage tissue consisting of biopolymer microstructured collagen-containing hydrogel, mesenchymal stromal cells of human adipose tissue (hADMSCs) and induction chondrogenic culture medium was prepared and placed in a perfusion bioreactor. As a result, on the 16th day of the study hADMSCs obtain a flattened shape typical for chondroblasts and demonstrate high proliferative activity with the formation of their own extracellular matrix. Histological analysis of the cultured system indicates the beginning of the formation of a tissue-engineered construct of human cartilage tissue.
Over the last decades mechanical circulation support has become one of the most effective treatment methods for patients with terminal heart failure. Unfortunately, in pediatrics this method is generally used on a short-term basis and includes, first of all, extracorporeal membranous oxygenation and left ventricular bypass by means of the extracorporeal centrifugal pumps. Nevertheless, using of these methods in children allowed considerably reducing mortality on the waiting list for heart transplant. Today, practically the only method of long term mechanical circulatory support in newborns and children at an early age being used is the system of paracorporeal artificial ventricles EXCOR, the usage of which results in larger problems of thrombosis. There is little clinical experience in using of the fully implanted systems developed for adults in older children. Therefore, as shown in the present review, the problem of creating long term circulatory support systems for newborns and younger children on the basis of the implanted pumps continues to be relevant.
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ARTICLES
HISTORY AND PHILOSOPHY
The first human heart transplant immediately exposed many unsolved problems of organ transplant existing at an early stage of the development of that kind of medical technology. The review of historical, legal and philosophical aspects of the first human heart transplantation in Russia and abroad is presented. Special attention is paid to the role and destiny of the pioneers of heart transplantation. The dramatic lives of Vladimir Demikhov and famous South African surgeon Christiaan Barnard are compared. The hard way of the heart transplantation founders is not lost, worthy successors continued their work, saving the lives of hundreds and thousands of patients.
ORGANIZATION AND ECONOMY
In this article, the authors defined the procedure for maintaining the material and technical base of medical centers providing high-tech assistance (especially, transplant care) to Russian citizens. The current regulatory and methodological base determining the procedure for repairs of fixed assets is evaluated, the main issues of capital repair planning in budgetary medical centers providing high-tech medical care are considered. The innovations introduced at the present time into the legislation determining the procedure for capital repairs are defined; the applicable concepts and scope of regulation are disclosed; the procedure for the implementation of major repairs in accordance with the current regulations is considered; the key issues that make it difficult to start capital repairs of the premises in budgetary medical centers providing high-tech medical care to Russian citizens are identified. Administrative and financial discipline while ensuring the working conditions of the material and technical base has been strengthened. Considerable attention should be paid to the medium-term planning of works, preparation of technical documentation, and procurement of funds for preparatory works. Whereas it is necessary to coordinate such decisions with the Ministry of Healthcare of Russia and other governmental institutions in Russia the timing of the implementation of such projects has significantly increased.