Organs For Transplantation Research Articles

A First Experience of Distant Lung Preservation for Transplantation in the Russian Federation.

Lung transplant is an effective method of treating patients with end-stage respiratory diseases, but problems such as the imbalance between the number of donor organs and the number ofrecipients needing organs still play a leading role. From a transplant point of view, a multiorgan donor is considered of greatest efficiency, so that all organs that can potentially be used should be transplanted. The combination of the vast geographical territory of Russia, the shortage of actual donors, and the relatively small number of transplant centers has led to the need to transport donor lungs by air over long distances. There were already precedents in the world for remote preservation of donor organs for transplant. In this study, we have described the unique experience of remote evaluation of donor lungs with their subsequent air transportation and transplantation, which is the first such description in Russia to our knowledge. The donor lungs for lung transplant were brought from medical institutions of the Samara region to Moscow. During remote evaluation, all information was transmitted to the transplant center by providing access to the automated information system "Organ Donation," which was used at that time by the service and contained all information about a potential donor in real time. The 2 transplant candidates had end-stage cystic fibrosis and severe respiratory failure; both patients underwent organ implantation from donors located outside their regions. In conditions of shortages of donor organs, long-distance transportation is a reasonable, feasible, and safe procedure.

A Remarkable Journey of Porcine to Human Xenotransplantation

Xenotransplantation of pig hearts offers a potential solution to the scarcity of available human organs for transplantation. This abstract explores the challenges and risks associated with xenotransplantation, as well as the ongoing research and development efforts aimed at overcoming these obstacles. The primary hurdle in pig-to-human heart transplantation is immunological compatibility, as the human immune system perceives pig organs as foreign and mounts a rejection response. Genetic engineering techniques are being investigated to modify pig organs and enhance compatibility with the human immune system. In addition, the risk of cross-species disease transmission, known as xenozoonosis, poses another concern. Researchers are actively working to identify and address these risks to ensure the safety of xenotransplantation. Although xenotransplantation of pig hearts is still in the experimental stage and not widely performed in clinical settings, numerous preclinical studies and clinical trials are underway to evaluate the safety and efficacy of the procedure. This abstract emphasizes the importance of ongoing research and development in the field, highlighting the potential of xenotransplantation as a viable solution for the organ shortage crisis. Ultimately, further advancements are necessary before xenotransplantation of pig hearts can be established as a routine clinical procedure.

Non-Donors of Organs and Tissues Due to Medical Refusal in a Transplant Referral Service

Obtaining organs for transplants through a deceased donor occurs exclusively through donation. However, some open protocols with potential donors do not become effective donors due to medical refusal. Our aim was to identify the profile of non-donors of organs and tissues due to medical refusal in a state reference service for transplants. This is a cross-sectional study with retrospective data collection from medical records of patients who died and had a protocol opened to evaluate brain death and procurement of organs and tissues in 2019. The sample consisted of 27 patients, the majority of whom were female, aged over 71 years, had primary education, and were married. The main causes of medical refusal were age above the recommended age and septicemia. Brain death was mostly confirmed within 12 hours, and the main cause of hospitalization was a vascular event. Identifying the profile of non-donors due to medical refusal is necessary for services to identify possible misattributed medical contraindications and thus contribute to reducing the disproportion between supply and demand for organs and tissues for transplants.

Moving Boundaries for Improving Organ Transplant Availability.

This brief overview is designed to address the options for increasing organ transplant rates to between 100 and 120 transplanted organs per million population globally. The focus of this review is the data produced through the World Health Organization's Global Observatory on Donation and Transplantation, with consideration for the issues that different countries need to address to achieve higher transplant rates. Without both optimized living donation and optimized deceased donation, rates of transplant are not sufficient to provide for a level of self-dependency for transplant therapy. Deceased donation comprises both donation from donors declared dead after cessation of all functions of the brain and donors declared dead from irreversible cessation of circulation of the blood. The preservation strategies that hold the greatest chance of increasing the utility of marginal and older donors involve normothermic circulation to prevent ischemic damage and potentially restore function of damaged organs. Normothermic in situ perfusion of abdominal organs has demonstrated utility, and consideration must be given to normothermic perfusion of the thoracic organs to improve heart and lung transplants, but this may challenge the legal definitions of death. Each nation must endeavor to increase organ donation capacity across the spectrum of donor types and must address the opportunities that normothermic perfusion of organs at retrieval may offer to alleviate shortages of organs for transplant and provide selfdependency for the communities.

63 Allogeneic Recellularized Lung Orthotopic (ARLO) Transplant Research

OBJECTIVES/GOALS: As of 2021, the lung transplantation waiting list has a mortality rate of 7.6 deaths per 100 patient-years. Bioengineered human organs is an emerging field of tissue engineering with a goal of developing suitable organs for transplantation. The focus of the project is to evaluate the efficacy of bioengineered lungs using a human-to-swine model. METHODS/STUDY POPULATION: This project will involve designing and assessing the bioengineered lung by establishing a human-to-pig xenotransplantation survival model. The project aims to evaluate how well the bioengineered lung functions within a living model. The bioengineered lung is constructed using swine connective tissue scaffolding, which has been recellularized with human cells. Anatomically, the lung will resemble a swine lung but will possess the immunological and cellular markers of human tissue. The proposed model will initially assess the immunological response of swine to human lung tissue. Lung function will be assessed during surgery using pulmonary vein gas samples and tissue sampling. Following the end of the study, additional tissues samples will be taken to evaluate the immunological response to the tissue. RESULTS/ANTICIPATED RESULTS: Xenotransplantation and bioengineered organs are two new emerging fields of research that have just begun to enter the large animal testing phase. This model will provide a novel human-to-pig xenotransplant survival model that will be used to test the efficacy of bioengineered lungs function in a dynamic living organism. The design has taken the principles of immunology learned from the current clinical and xenotransplant research and has incorporated this knowledge into the known pig-to-pig transplant models. We anticipate that this model design will be easily reproducible and can be expanded to other bioengineered organs as an effective means to test functionality. DISCUSSION/SIGNIFICANCE: The COVID-19 pandemic’s aftermath may lead to an increased demand for lung transplants. Bioengineered lungs could provide an additional source of organs to supplement current availability. This novel approach has the potential to offer a means to test several different types of bioengineered organs in the future.

En bloc Kidney Transplant – A Surgical Illustration and Clinical Experience from a Tertiary Care Hospital in South India

There is a global shortage of transplantable organs, especially in a resource-limited country like India. Deceased pediatric donors provide an excellent opportunity to expand the donor pool. Herein, we report a rare case of multi-organ harvesting from a 3-year-old brain-dead donor, where both the kidneys were transplanted en bloc to an adult male recipient and the liver to a 4-year-old male child. This case report provides the surgical steps and our experience.

Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity

Three-dimensional liver bioprinting is an emerging technology in the field of regenerative medicine that aids in the creation of functional tissue constructs that can be used as transplantable organ substitutes. During transplantation, the bioprinted donor liver must be protected from the oxidative stress environment created by various factors during the transplantation procedure, as well as from drug-induced damage from medications taken as part of the post-surgery medication regimen following the procedure. In this study, Silymarin, a flavonoid with the hepatoprotective properties were introduced into the GelMA bioink formulation to protect the bioprinted liver against hepatotoxicity. The concentration of silymarin to be added in GelMA was optimised, bioink properties were evaluated, and HepG2 cells were used to bioprint liver tissue. Carbon tetrachloride (CCl4) was used to induce hepatotoxicity in bioprinted liver, and the effect of this chemical on the metabolic activities of HepG2 cells was studied. The results showed that Silymarin helps with albumin synthesis and shields liver tissue from the damaging effects of CCl4. According to gene expression analysis, CCl4 treatment increased TNF-α and the antioxidant enzyme SOD expression in HepG2 cells while the presence of silymarin protected the bioprinted construct from CCl4-induced damage. Thus, the outcomes demonstrate that the addition of silymarin in GelMA formulation protects liver function in toxic environments.

Is Time Scheduling Important? An Analysis of Donor Heart Cross-clamp Times During Heart Transplantation.

Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3). Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.

Legal regulation of human somatic rights: transplantation of human organs and biological tissues in Ukraine and foreign countries

The article examines the problems of legal regulation of transplantation of organs and tissues of the human body in Ukraine and foreign countries. Emphasis is placed on legal and ethical difficulties arising in the field of transplantology. It is noted that the right to «mechanize the body» has a number of specific features, namely: the specific nature of the object of these rights - the human body, which is the object of property rights and currently has mainly a monetary value expression; natural dependence on knowledge of biology, genetics, medicine, technology. Their existence and implementation are possible only with the help of achievements of scientific and technical progress; novelty, which has a different degree of expression, depending on the type of protected result of disposal of body or life; ambiguous attitude from the side of religion, morality, ethics, politics; inextricable connection with constitutional (fundamental) human rights in view of the special connection with personal (natural) rights and the peculiarity as an independent group of human rights; exclusivity in terms of its legal consequences in the process and as a result of their implementation. With any change in the physical embodiment of a person, the subjective aspect of legal relations changes, that is, many connections of various branches of legal regulation (civil, marital and family, constitutional, etc.) are affected; the degree of their recognition and implementation reflects the level of development of the state and society in general, etc. It is emphasized that individual somatic rights are reflected both in the legislation of Ukraine and in the legislation of foreign countries. For example, the right to transplant organs in national legislation is not used as a right to dispose of one's body, but as a certain necessity, a medical indication. In order to regulate the issue of organ donation, the legislation of individual states prescribes the practice of establishing special procedures for obtaining the donor's consent to extract a transplant from him (Belgium, Greece, Turkey). Given the lack of transplants for transplant operations, it is important to develop educational work at the state level, explaining to citizens the need to issue voluntary consents for the posthumous use of their donor material. It is worth making proposals for the development and adoption of the State Program of Ukraine aimed at the development of donation. This program should provide organizational, legal and preventive state measures for the promotion and development of legal donation in Ukraine; proposals for the development of a national legal mechanism aimed at encouraging voluntary posthumous donation, which would be based on the lifetime legally formalized consent of potential donors to the posthumous free use of their donor material.

Developing Guidance for Donor Intervention Randomized Controlled Trials: Initial Discussions From the Canada-United Kingdom 2022 Workshop.

Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs). With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field. Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations. Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs.

Beyond the Final Heartbeat: Neurological Perspectives on Normothermic Regional Perfusion for Organ Donation after Circulatory Death.

Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required. ANN NEUROL 2024;95:1035-1039.

O176: Complement inhibition enhances hepatocyte viability in a cell model of transplant ischaemia reperfusion injury

Abstract Background Liver transplantation is limited by the number of optimal organs for transplantation. Ischaemia reperfusion injury (IRI) plays a key role in the utilisation of organs for transplantation - many organs are still not used due to concerns over viability. We evaluated the C5 inhibitor Eculizumab (EZB) in a cell model of IRI. Methods HepG2 cells, an immortalised hepatocyte cell-line, were utilised to model IRI. Cells were incubated in an anoxic chamber to model 'ischaemia' and then 'reperfused' in a normoxic incubator for 4 and 1 hours, respectively. The incubation media was supplemented with perfusate from donation after circulatory death (DCD) livers that had undergone standard normothermic machine perfusion (n=2) and EZB treated perfusate (n=2). Results The IRI model reduced cell viability and proliferation (p≤0.05). However, the model created no significant changes in the production of biomarkers VEGF, IL-10, IL-8, GDF-15 and ROS (p&amp;gt;0.05). Notably, EZB therapy significantly increased anti-inflammatory IL-10 production (p≤0.0001) and expression (p≤0.001), whilst enhancing cell viability and proliferation (p≤0.0001). Conclusion The complement system may play an important role within IRI and complement inhibition is a promising treatment for DCD livers, as demonstrated by treatment of cells with EZB therapy. Further work is required to optimise the models and treatment strategy before clinical testing.

Organ Procurement From Foreigners Who Died in Poland and Organ Transplantation to Foreigners

The aim of the work was to present data concerning organ donation from and transplantation to foreigners in Poland. Data came from registries maintained by the Polish Transplant Coordinating Center POLTRANSPLANT, consisting of the national waiting list, deceased donor registry, transplant registry, and live donor registry. In Poland, the rules for organ and tissue procurement for transplantation from foreigners who died in Poland and the rules for transplanting organs to foreigners are adopted and applied. Before the outbreak of the war in Ukraine, "cross-border" cases of donations and transplants were rather sporadic. After the outbreak of the war, due to the mass influx of Ukrainian citizens, the situation changed, and the participation of foreigners (mostly Ukrainians) in transplantation procedures increased significantly and, in 2022, accounted for the total number of events: approximately 4% in the case of donation, slightly over 1% in the case of qualifications for transplantation and almost 2% in the number of transplantations performed. Despite this increase, the number of events is not high or critical and does not affect the efficiency of organ transplantation medicine in Poland.

Platform for Organ Donation and Transplantation using Blockchain

The critical shortage of organs for transplantation necessitates exploring innovative solutions to improve the matching and allocation process. Blockchain technology, with its significant principles of decentralization, security, and transparency, presents a promising avenue for building a more efficient and trustworthy platform for organ donation and transplantation. This paper surveys the current state of organ donation systems, explores the potential benefits of blockchain integration, and analyzes existing research on blockchain-based platforms for this domain.

Organ Donation from Patients Receiving Extracorporeal Membrane Oxygenation: A Systematic Review

The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors. Systematic literature review (Scopus and PubMed, up to October 11, 2023). All study designs. Organ recipients from patients on ECMO at the time of death. Outcome of organ donation from ECMO donors. The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years. Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage.

Knowledge, Attitudes and Intention to Donate Organs among the Public, Health Sciences Students and Health Personnel: A Scoping Review with a Systematic Review of Malaysian Studies.

Various barriers lead to a shortage of organs for transplantation in Malaysia. One drive to improve the organ donation rate operates through future healthcare practitioners and practitioner advocacy. This scoping review was carried out to establish and summarise findings about organ donation-related articles among the public, health sciences students and health personnel. A further aim was to synthesise the latest data on knowledge and attitudes towards organ donation in the Malaysian population. PubMed, Scopus, Google Scholar and the Malaysian Medical Repository (MyMedR) were used for a search conducted up to May 2022. Relevant search terms included 'Organ donation' and 'Malaysia'. Journal articles related to knowledge, attitudes and intention were grouped under the general public and health science. Students and health personnel were included. Eligible studies were reviewed by two independent reviewers. Any disagreements were resolved by consensus with a third reviewer. The 31 included articles revealed an increased level of awareness among the public regarding organ donation. The analysis identified that nonrecognition of brainstem death (38.5%), no knowledge of how to contact the Organ Transplant Coordinator (82.3%) and never approaching the families of a potential donor (63.9%) led to a lack of confidence among healthcare practitioners to promote organ donation. The shortage of organ donors is the result of the failure to identify the expected donor, obtain consent and procure the organs due to the passivity of Malaysian health professionals in promoting the organ donation process.

A Split-Lung Ex Vivo Perfusion Model for Time- and Cost-Effective Evaluation of Therapeutic Interventions to the Human Donor Lung.

With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed. A split-lung EVLP model, which allows stable perfusion and ventilation of two single lungs from the same donor, offers advantages scientifically, financially and in time to yield results. Identical parallel circuits allow one to receive an intervention and the other to act as a control, removing inter-donor variation between study groups. Continuous hemodynamic and airway parameters are recorded and blood gas, perfusate, and tissue sampling are facilitated. Pulmonary edema is assessed directly using ultrasound, and indirectly using the lung tissue wet:dry ratio. Evans blue dye leaks into the tissue and can quantify vascular endothelial permeability. The split-lung ex vivo perfusion model offers a cost-effective, reliable platform for testing therapeutic interventions with relatively small sample sizes.

The value of organ and tissue biovigilance: a cross-sectional analysis.

Biovigilance (BV) systems aim to improve the quality and safety of tissues and organs for transplantation. This study describes the Catalan BV system and analyzes its utility. It is a retrospective analysis of notifications on serious adverse events (SAEs) and reactions (SARs) since the implementation of the BV system (2008 for tissues and 2016 for organs) until 2020. Variables are presented to describe the most common critical steps of the pathway and complications associated with the quality and safety of tissues and organs. A total of 154 and 125 notifications were reported to the Tissue and the Organ BV systems, respectively. Most SAEs were related to unexpected donor diseases and implemented actions were assured on those deemed preventable. Regarding SARs, donor-transmitted infections and malignancies (only organs) were the most common, followed by graft failure (tissues) and process-related (organs). The incidence of SAEs and SARs related to tissue was 3.44‰ and 0.22‰, respectively. The corresponding figures for organs were 31.48‰ and 8.8‰, respectively. The analysis of the notifications to the Catalan BV systems has provided useful information about existing risks associated with the quality and safety of tissues and organs, and enabled the implementation of actions targeted to diminish risks and mitigate damage.

The Promise of Complement Therapeutics in Solid Organ Transplantation.

Transplantation is the ideal therapy for end-stage organ failure, but outcomes for all transplant organs are suboptimal, underscoring the need to develop novel approaches to improve graft survival and function. The complement system, traditionally considered a component of innate immunity, is now known to broadly control inflammation and crucially contribute to induction and function of adaptive T-cell and B-cell immune responses, including those induced by alloantigens. Interest of pharmaceutical industries in complement therapeutics for nontransplant indications and the understanding that the complement system contributes to solid organ transplantation injury through multiple mechanisms raise the possibility that targeting specific complement components could improve transplant outcomes and patient health. Here, we provide an overview of complement biology and review the roles and mechanisms through which the complement system is pathogenically linked to solid organ transplant injury. We then discuss how this knowledge has been translated into novel therapeutic strategies to improve organ transplant outcomes and identify areas for future investigation. Although the clinical application of complement-targeted therapies in transplantation remains in its infancy, the increasing availability of new agents in this arena provides a rich environment for potentially transformative translational transplant research.

Multiscale embedded printing of engineered human tissue and organ equivalents

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.