Organs For Transplantation Research Articles

Advanced cryopreservation as an emergent and convergent technological platform

Advanced cryopreservation technologies have the potential to transform organ transplants, biomedical research, food storage, aquaculture, biodiversity repositories, ecological restoration, and numerous other applications. These surpass the capability of existing cryopreservation technologies to extend the life and viability of biological materials at various scales from cells to tissues, organs, and entire organisms. In this article, we demonstrate why innovations in advanced cryopreservation, which we analyze as emergent, convergent platform technologies, raise novel concerns for research ethics and coordination, governance, and equitable access to benefits. As emerging technologies, they may disrupt markets or destabilize social institutions, including the systems that govern the distribution of organs for transplant. As convergent technologies, their impact will be heightened through interaction with other technologies. The technologies that may intensify the social and ethical effects of advanced cryopreservation include information technologies that permit the administration of complex logistics of storage and transport, biotechnologies for the management of floral and faunal species and populations, and 3D printing technologies that may enable the development and distribution of customizable peripheral components of this platform technology. The speed of development among diverse applications of the core platform is likely to vary between sectors in ways that are responsive to public support as well as to ethical constraints, and advancements in any sector will affect the achievement of reliability for the core technology across sectors. We recommend that societal benefits and risks be assessed both in the specific contexts for which peripheral components are developed and for the core technology.

Challenges and Opportunities in Deceased Organ Donation Program: Insights from a Tertiary Care Hospital in South India

Background: Organ transplantation is a critical medical intervention for patients with end-stage organ failure. Deceased organ donation plays a pivotal role in meeting the demand for organs. However, there exists a significant disparity between the need for organs and their availability, especially in low-income countries. India, despite its potential donor pool, faces a severe shortage of organs for transplantation. Materials and Methods: This retrospective study analyzed hospital records of 116 potential deceased organ donors from 2013 to 2020. Data encompassed demographics, next-of-kin consent for organ transplantation, and circumstances of injury. Results: Results revealed that 85.34% of potential donors were men, and 14.66% were women. After counseling, 71.55% (83/116) of the families consented to deceased organ donation. Most potential donors fell within the 21–30 age group (25.88%). The majority of donors (80.17%) died due to road traffic accidents (RTAs), primarily two-wheeler drivers constituted the largest group of deceased (51.72%). Conclusion: Bridging the gap between organ demand and supply in India necessitates addressing the lack of awareness regarding brain death and organ transplantation. Collaborative efforts involving NGOs, healthcare institutions, media, and government bodies are essential to raise awareness and improve donation rates, especially in public health centers. Establishing guidelines for compassionate discussions with families about organ donation is imperative.

ACOMPANHAMENTO DE PACIENTES PORTADORES DE CIRROSE HEPÁTICA E OS DESAFIOS DA GESTÃO

Introduction: Liver cirrhosis is a chronic condition in which liver cells are destroyed or compromised, leading to the formation of scars, nodules or fibrosis. This factor contributes to a decrease in the partial or total functioning of the organ. Objectives: The main objective of this study was to investigate the challenges faced by management in the treatment and monitoring of patients with liver cirrhosis. Methodology: This is an integrative review of the literature searched in the following databases: PUMED and Virtual Health Library (VHL/SCIELO) between the years 2019 to 2023. Results: After the search and selection according with the inclusion and exclusion criteria, 09 articles were selected to compose this study. Conclusion: Public management faces challenges related to the shortage of specialized professionals, unequal distribution of these professionals and limited financial resources, along with restrictions on organs for liver transplantation. To face such obstacles, it is vital to prioritize the integration of health services, the efficient allocation of resources and the implementation of policies that raise awareness among the population about the causes and importance of early detection of the disease. These measures aim to ensure timely and effective treatment, in addition to improving the quality of life of patients with liver cirrhosis.

Xenotransplantation ethical and legal challenges

This work examines xenotransplantation, a rising medical practice that seeks to mitigate the shortage of organs for transplantation. Xenotransplantation essentially involves the transfer of organs, tissues, or cells from animals to humans and represents a promising medical solution. The research will focus on the potential benefits of this technique, highlighting its crucial role in saving lives and improving the quality of life for future patients The analysis will cover aspects of xenotransplantation in Brazil and the experiences of xenotransplantations already conducted worldwide, aiming to understand the scope of the problems and challenges faced by patients and healthcare professionals. The study will seek to understand various perspectives on xenotransplantation, considering the views of different authorities and experts in the field. Finally, it will examine the demand for transplants in Brazil and address issues related to public policies, legislative aspects, and resolutions of competent bodies, to comprehend how xenotransplantation practice is regulated in Brazil.

Perspective on donor-derived infections in Italy.

Expected and unexpected donor-derived infections (DDI) are a rare event in solid organ transplant (SOT) recipients but are potentially associated with significant morbidity and mortality. To assure the microbial safety of transplantation, both national guidelines and the current, regional, and local epidemiology of infectious diseases must be considered. In the present paper the strategies adopted by the Italian National Center for Transplantation (CNT) since 2003 and their evolution to guarantee the safety of organ transplantation are reported. Starting in 2012 mandatory reporting to the CNT of all adverse reactions was started. The number and type of DDI reported to the CNT are currently being analyzed. The infectious diseases second opinion has written and updated the guidelines on the safety of organs for transplantation and supported the Italian transplant network for the use of organs from donors with suspected or documented potentially transmissible infections. A transplant safety network was developed in Italy in 2003 and has been updated according to the evolving knowledge and the changing epidemiology. This is an evolving field, and a continuous update of the recommendation is needed.

On the Possibilities and Significance of Unmanned Aerial Vehicles for the Pre- Hospital Stage of Medical Care

Unmanned aerial vehicles are an important force in search and rescue operations. They help reduce the time needed to search for and provide assistance to the wounded, sick and injured who are located at a large territorial distance and in hard-to-reach places. With the help of computer “vision” and sensors such as noise sensing, binary sensing, vibration and thermal sensing, drones are able to search for living patients not only in the sea, high in the mountains and in mines, but also buried under the rubble of buildings and structures. Such devices demonstrate advantages in emergency and urgent delivery of medical resuscitation and other medical equipment, medicines, blood products and organs for transplantation to patients, especially those in remote locations. With the help of drones, it is possible to effectively sort patients in case of mass sanitary losses, carry out disinfection and remotely monitor the health status of patients with highly contagious infectious diseases and other pathological conditions, as well as reduce the time for providing other medical and humanitarian services to the population. It is obvious that the use of drones requires further study of their promising capabilities, especially in the actual conditions of emergency medical services.

Evaluating different methods for kidney recellularization

This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation stands as the optimal option, yet the scarcity of organs persists. Employing tissue engineering, researchers sought to assess the feasibility of generating kidneys for transplantation. Pig kidneys were utilized since they possess higher similarities to human kidneys. Cells were removed via decellularization, which maintains the organ’s microarchitecture. Subsequently, pig kidney cells and human red blood cells were perfused into the vacant kidney structure to reconstitute it. The methodologies employed showed promising results, suggesting a viable approach to increase the recellularization rate in whole pig kidneys. This proof-of-concept establishes a groundwork for potentially extending this technology to human kidneys, tackling the organ shortage, thus positively enhancing outcomes for ESRD patients by increasing the availability of transplantable organs.

Generation of human-pig chimeric renal organoids using iPSC technology

Porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation have garnered attention, but both face technical challenges. Interspecies chimeric organ production using human iPSCs shows promise in overcoming these challenges. Our group successfully generated chimeric renal organoids using human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology is limited to rodents. Therefore, this study focused on producing human-pig chimeric renal organoids, as pigs are the most promising species for xenotransplantation. Modification of existing culture systems enables continuous renal development in both species, resulting in the successful creation of human-pig chimeric renal organoids. Moreover, this method can be applied to generate humanized xenogeneic kidneys for future clinical applications. This study provides evidence that optimizing culture conditions enables the early-stage kidney development beyond species barriers, thus laying the foundation for accelerating research on humanized xenogeneic kidney fabrication for clinical purposes.

Assessing Biomarkers of Porcine Kidneys under Normothermic Machine Perfusion-Can We Gain Insight into a Marginal Organ?

To identify potentially transplantable organs in a pool of marginal kidneys, 33 porcine slaughterhouse kidneys were perfused for 4 h with whole blood. During the normothermic perfusion, plasma, urine, and tissue samples were taken. Several biomarkers for tubule injury, endothelial activation, and inflammatory response were evaluated for a potential correlation with macroscopic appearance, histology, and filtration activity. Generally, biomarker levels increased during perfusion. TLR-4, EDN-1, and NGAL were not associated with any classification. In contrast, a steeper increase in NAG and IL-6 in plasma correlated with a poor macroscopic appearance at 4 h, indicating a higher inflammatory response in the kidneys with worse macroscopy early on, potentially due to more damage at the tubules. Although long-term effects on the graft could not be assessed in this setting, early observation under machine perfusion with whole blood was feasible. It allowed the assessment of kidneys under conditions comparable to reperfusion. This setting could give surgeons further insight into the quality of marginal kidneys and an opportunity to pre-treat them.

Pig-to-human kidney xenotransplants using genetically modified minipigs

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both Tcell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

Navigating the Ethical Landscape of Xenotransplantation: A Metadata Analysis for Informed Decision-Making

Background: Xenotransplantation, the transfer of animal organs into humans, has gained attention as a solution to the global shortage of human organs for transplantation. Genetic advancements in donor animals, particularly pigs, offer potential to reduce immune rejection and improve compatibility.Objective: This review aimed to examine the scientific advancements, ethical concerns, and clinical outcomes of xenotransplantation, focusing on the use of genetically modified pigs.Methods: A review based on metadata analysis was conducted, adhering to PRISMA guidelines. The research question focused on the efficacy, safety, and ethical considerations of xenotransplantation. Databases including PubMed, Scopus, and Cochrane Library were searched using keywords such as "xenotransplantation," "genetic modification," "pig organ transplantation," and "immune rejection." Studies were screened based on eligibility criteria, including clinical trials and ethical analyses. Quality was assessed using the CASP tool, and data were synthesized from 27 studies.Results: Xenotransplantation from genetically modified pigs showed a reduction in immune rejection rates by 60% and decreased waiting times for organ transplants by up to 50%. Long-term graft survival remains uncertain, with a success rate of 70% in short-term trials.Conclusion: Xenotransplantation offers a promising solution to organ shortages, but further long-term studies and ethical evaluations are needed to ensure safety and acceptance.

Small Donors, Big Impact: Optimizing Organ Utilization in Simultaneous Pancreas and Kidney Transplantation From Extra Small Pediatric Donors.

Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis. This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20kg. All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival. This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates.

246.8: How to increase the number of donors and organs for transplantation using a systematic evaluation of potential deceased donors?

246.8: How to increase the number of donors and organs for transplantation using a systematic evaluation of potential deceased donors?

Enhancing Donor Transport Success: Lessons From the Iranian Experiences.

Organ transplant is a complex process that involves various medical, legal, and social factors. The organ demand continues to outweigh the supply, leading to global challenges in the expansion of transplant programs. Ischemic time is crucial for the viability of organs, and efforts are being made to reduce transport time to improve transplant success rates. The viability and quality of the organ for transplant depends on minimized ischemic time. A new method is presently being implemented in Iran, in which, instead of transfer of organs, leading to reduced organ quality due to ischemic time, the donors themselves are transferred to transplant centers with the help of a trained team after brain death is confirmed and with the consent of the family. During the transfer process, an anesthesiologist or nurse specialized in donor care performs the relevant pretransplant procedures. The successful transportation of donors to centers for organ procurement requires meticulous planning, trained personnel, and adherence to safety protocols. Quality assurance measures, including audits and safety protocols, are in place to ensure the timely and safe delivery of donated organs. Ultimately, improvements in the transportation process for organ donation can enhance transplant success. Successful transportation of donors to organ procurement units is crucial for reducing ischemic time and improving the success rate and quality of organ transplants. Careful planning, communication, and collaboration among health care professionals are necessary for the timely and safe delivery of donated organs.

Rheological characterization and print quality studies of gelatin/collagen I/PEGDA hydrogels

Bioprinting is an up-and-coming technology that uses the basis of additive manufacturing and applies it to the field of tissue engineering. Bioprinting is used to create 3D models of diseased tissue and organs, test cellular responses to drug therapies, and create potentially transplantable organs and vasculature. Bioprinting has gained increasing interest especially in drug discovery, as the traditional 2D cell culture models have been shown to produce results that are not mimicked in animal and human trials. Bioprinters use materials called bioinks, developed from hydrogels which can contain cells and biological factors. While there are commonly used bioinks, there is a need for the development of a diverse range of bioinks for varying applications. In this study, an alternative bioink was developed. The formulations included gelatin, collagen I, and varying amounts of poly (ethylene glycol) diacrylate (PEGDA). These formulations were subject to rheological characterization and print quality analysis. Formulations with higher concentrations of PEGDA had higher degrees of shear-thinning, higher viscosity recovery, lower viscosities, and less dominant gel behavior. The print quality studies showed that the formulations with lower concentrations of PEGDA had better printability, print accuracy, and print fidelity. Formulation P5 had the best overall print quality.

Making organ donation after circulatory death routine: Preserving patienthood and reproducing ways of dying in the intensive care unit.

Controlled organ donation after circulatory death (DCD) was re-introduced in the UK in 2008, in efforts to increase rates of organs for transplant. Following reintroduction, there were debates about the ethics of DCD, including whether potential DCD donors receive end-of-life care which is in their best interests. Since this time, DCD has become a routine donor pathway in the NHS. In this article, we present findings from an ethnographic study examining the everyday practices of DCD in two English Trusts. Drawing on the concept of death brokering and Bea's (2020) call to consider organ donation as embedded and routine practice within health care, we look at how DCD is integrated into end-of-life care in intensive care units. We show how DCD is made routine at the end-of-life via the practices of health professionals who create an active separation between discussions about death and donation; reproduce usual ways of doing things in end-of-life care; and respect the distinction between patient/donor, dying and death. In doing so, we argue these function to preserve the patienthood of the potential donor, ensuring DCD operates as an integrated part, and culturally accepted form of, good end-of-life care for potential donors, their relatives, and health professionals alike.

Revolutionizing deceased donor transplantation: How new approaches to machine perfusion broadens the horizon for organ donation

Solid organ transplantation is lifesaving for persons with end-stage organ disease. Thanks to advancements in organ preservation, surgeons are now able to successfully transplant organs that were previously considered high risk for poor graft function. Innovations in perfusion machine types, preservation solutions and additives to preservation solutions have significantly improved the ability to utilize organs previously thought unusable.Newer organ preservation techniques are offering a promising outlook for extending graft longevity and improving transplant outcomes. This review explores the impact of deceased donor type on graft quality and highlights emerging strategies designed to improve the function and viability of deceased donor organs.

Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism

Interspecies blastocyst complementation holds great potential to address the global shortage of transplantable organs by growing human organs in animals. However, a major challenge in this approach is the limited chimerism of human cells in evolutionarily distant animal hosts due to various xenogeneic barriers. Here, we reveal that human pluripotent stem cells (PSCs) struggle to adhere to animal PSCs. To overcome this barrier, we developed a synthetic biology strategy that leverages nanobody-antigen interactions to enhance interspecies cell adhesion. We engineered cells to express nanobodies and their corresponding antigens on their outer membranes, significantly improving adhesion between different species' PSCs during invitro assays and increasing the chimerism of human PSCs in mouse embryos. Studying and manipulating interspecies pluripotent cell adhesion will provide valuable insights into cell interaction dynamics during chimera formation and early embryogenesis.

Healthcare Worker Attitudes to Living Donation Prior to Planned Withdrawal of Care.

This study assesses the attitudes of healthcare practitioners toward Living Donation Prior to Planned Withdrawal of Care (LD-PPW): the recovery of a living donor organ before withdrawal of life-sustaining measures in a patient who does not meet criteria for brain death, but for whom medical care toward meaningful recovery is deemed futile. An electronic survey was administered to 1735 members of the American Society of Transplant Surgeons mailing list with 187 responses (10.8%). Data from this study revealed that 70% of responding practitioners agreed with LD-PPW due to principles of beneficence and autonomy. Also, 65% of participants felt confident in their ability to declare the futility of care and 70% felt that LD-PPW should be added as an option when registering to become an organ donor. Currently, nearly half of all donation after circulatory determination of death do not proceed to donation. LD-PPW has been proposed as an alternative procedure targeted at increasing the quality and quantity of transplantable organs while respecting the donor's right to donate, though its implementation has been hindered by concerns over public and provider perception. This study revealed support for LD-PPW among healthcare practitioners as an alternative procedure to increase the quality and quantity of transplantable organs while respecting the donor's right to donate.

Machine perfusion in transplantation surgery

The use of machine perfusion in solid organ transplantation has developed tremendously worldwide in recent years. Although the number of randomized controlled trials in the field of organ preservation is still limited, machine perfusion has been shown to be superior to static cold storage of donor organs. Various devices for clinical use with hypothermia or normothermia are already available for most organs. Whether and which perfusion strategy is superior to the others is the subject of current clinical research. This also applies to the further evaluation of possible synergistic effects in the sequential use of the various protocols. The common goal of all dynamic perfusion technologies is to optimize organ preservation between removal and transplantation. By testing the quality of marginal donor organs prior to transplantation, it should also be possible to use these organs without exposing the patient to increased risk. This can lead to a significant expansion of the donor pool. This is particularly important in Germany, where there is an ongoing shortage of organs and restrictive legislation regarding the expansion of the donor pool. Furthermore, the perfusion technology offers the possibility to serve as a platform for other ex situ and in situ therapies on isolated organs. In addition to the conditioning of pre-damaged organs for transplantation, this could lead to further applications in the context of targeted organ therapies and also to improved transplant logistics in the future.