Organ Donation Research Articles

Optimized partial freezing protocol enables 10-day storage of rat livers

Preserving organs at subzero temperatures with halted metabolic activity holds the potential to prolong preservation and expand the donor organ pool for transplant. Our group recently introduced partial freezing, a novel approach in high-subzero storage at -15 °C, enabling 5-day storage of rodent livers through precise control over ice nucleation and unfrozen fraction. However, increased vascular resistance and tissue edema suggested a need for improvements to extend viable preservation. Here, we describe an optimized partial freezing protocol with key optimizations, including an increased concentration of polyethylene glycol (PEG) to enhance membrane stability while minimizing shear stress during cryoprotectant unloading with an acclimation period and a maintained osmotic balance through an increase in bovine serum albumin (BSA). These approaches ensured the viability during preservation and recovery processes, promoting liver function and ensuring optimal preservation. This was evidenced by increased oxygen consumption, decreased vascular resistance, and edema. Ultimately, we show that using the optimized protocol, livers can be stored for 10 days with comparable vascular resistance and lactate levels to 5 days, outperforming the viability of time-matched static cold stored (SCS) livers as the current gold standard. This study represents a significant advancement in expanding organ availability through prolonged preservation, thereby revolutionizing transplant medicine.

A multicenter observational study to establish practice for circulatory death declaration for organ donation in South Korea

Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death.

Future directions in transmasculine genital gender-affirming surgery: tissue substitutes and transplant.

The present study reviews contemporary literature focused on transplantation and tissue substitutes for the purposes of masculinizing genital gender affirming surgery. Additional background is provided for both topics to provide a more comprehensive understanding of the modern applications. Genitourinary vascularized composite allotransplantation has become a reality in recent years with several cases reported worldwide in cisgender men with promising reports of urinary and sexual function. A natural extension might be to apply these techniques to gender affirming surgery (GAS). Technical barriers include anatomic differences between vasculature supporting penoscrotal and vulvovaginal anatomy as well as size discrepancies between the corporal bodies which complicate the required anastomoses. Whether the smaller caliber of biologic female pelvic vasculature can support erection of a neophallus is another obstacle. Ethically, resource allocation, elective immunosuppression, society response to organ donation and gender identity, as well as the psychosocial safety of the patient given charged public opinion must all be considered.Tissue substitutes have long been used in urologic reconstruction but more recently applied to masculinizing gender affirmation surgery which has traditionally relied on autografting. The focus has been on restoring form and function to the donor site as well as facilitating treatment of urethral stricture and wound complications after phalloplasty. Furthermore, aesthetic applications have also been described, most recently for glans atrophy. The field of masculinizing gender affirmation surgery represents an exciting frontier for surgeons and patients alike. Given the relative nascency of the specialty and its propensity to draw techniques from various surgical disciplines there exists a unique opportunity for rapid innovation to overcome challenging problems posed by these complex procedures as evidenced by discussions around applying penile transplantation and the use of novel tissue grafting techniques.

HeartMate III Autonomy Assistant in a Hemiplegic Left Ventricular Assist Device Patient: A Case Report.

Terminal heart failure presents challenges, requiring cardiac transplantation, or mechanical circulatory support. Limited donor organ availability has made mechanical support crucial. Advances in centrifugal-flow systems, compared to axial-flow, have improved patient outcomes by reducing adverse events. Rehabilitation is vital for patient independence postimplantation. We developed a tool to aid hemiplegic patients in managing power sources. A 44 year old male with tritroncular ischemic heart disease and a 15% ejection fraction. He underwent a double bypass and left ventricular assist device (LVAD) implantation while awaiting a transplant. Postsurgery, the patient suffered a stroke, leading to left motor impairments. To assist in managing LVAD power sources, an autonomous tool with a Woodcast support base and antislip surface was developed. The tool improves autonomy and quality of life for motor-impaired patients. It is designed to be portable, adaptable, supporting various mobility levels. Real-world evidence shows it reduces time and alarms for battery changes, proving effective in home settings. The tool significantly enhances hemiparetic patients' self-care and independence, showing promise for motor-impaired individuals. Further research is needed to evaluate long-term benefits and challenges.

What Does the Evaluation of the Organ Donation (Deemed Consent) Act 2019 in England Tell Us About the Effectiveness of Deemed Consent Systems for Deceased Organ Donation?

What Does the Evaluation of the Organ Donation (Deemed Consent) Act 2019 in England Tell Us About the Effectiveness of Deemed Consent Systems for Deceased Organ Donation?

Enhancing differentiation and functionality of insulin-producing cells derived from iPSCs using esterified collagen hydrogel for cell therapy in diabetes mellitus

BackgroundIslet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for β-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels.MethodsiPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques.ResultsEsterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups.ConclusionEsterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic β-cells, advancing cell therapy in diabetes cell therapy.

Supporting Financial Neutrality in Donation of Organs, Cells, and Tissues.

The avoidance of financial gain in the human body is an international ethical standard that underpins efforts to promote equity in donation and transplantation and to avoid the exploitation of vulnerable populations. The avoidance of financial loss due to donation of organs, tissues, and cells is also now recognized as an ethical imperative that fosters equity in donation and transplantation and supports the well-being of donors and their families. Nevertheless, there has been little progress in achieving financial neutrality in donations in most countries. We present here the findings of an international ethics working group convened in preparation for the 2023 Global Summit on Convergence in Transplantation, held in Santander, Spain, which was tasked with formulating recommendations for action to promote financial neutrality in donation. In particular, we discuss the potential difficulty of distinguishing interventions that address donation-related costs from those that may act as a financial incentive for donation, which may inhibit efforts to cover costs. We also outline some practical strategies to assist governments in designing, implementing, and evaluating policies and programs to support progress toward financial neutrality in donation.

Developing and Expanding Deceased Organ Donation to its Maximum Therapeutic Potential: An Actionable Global Challenge From the 2023 Santander Summit.

On November 9 and 10, 2023, the Organización Nacional de Trasplantes (ONT), under the Spanish Presidency of the Council of the European Union, convened in Santander a Global Summit entitled "Towards Global Convergence in Transplantation: Sufficiency, Transparency and Oversight." This article summarizes two distinct but related challenges elaborated at the Santander Summit by Working Group 2 that must be overcome if we are to develop and expand deceased donation worldwide and achieve the goal of self-sufficiency in organ donation and transplantation. Challenge 1: the need for a unified concept of death based on the permanent cessation of brain function. Working group 2 proposed that challenge 1 requires the global community to work toward a uniform, worldwide definition of human death, conceptually unifying circulatory and neurological criteria of death around the cessation of brain function and accepting that permanent cessation of brain function is a valid criterion to determine death. Challenge 2: reducing disparities in deceased donation and increasing organ utilization through donation after the circulatory determination of death (DCDD). Working group 2 proposed that challenge 2 requires the global community to work toward increasing organ utilization through DCDD, expanding DCDD through in situ normothermic regional perfusion, and expanding DCDD through ex situ machine organ perfusion technology. Recommendations for implementation are described.

Expanding Opportunities for Living Donation: Recommendations From the 2023 Santander Summit to Ensure Donor Protections, Informed Decision Making, and Equitable Access

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Reinforcing Global Oversight of Organ Transplantation: Activity and Outcome Monitoring Through the Development of Registries.

Establishing transparency and oversight of organ transplantation by regulatory agencies is of paramount importance to assure ethical, legal, and clinically robust transplantation practices. Registries reporting activity and outcome data of the donor and recipient, including donor source (living or deceased), must be developed for each transplant and should be a mandatory requirement to achieve accreditation to perform transplant surgeries. Collected data for the living organ donor must include the nationality, the nature of their relationship with the recipient, and the complications encountered by living donors that result in prolonged morbidity or mortality. Long-term patient and graft survival must be reported for the recipient with the underlying reasons for mortality or graft loss. To retain the authorization to perform organ transplantation, a facility must ensure that it reports this required information regarding every organ transplant.

Recent Progress on Organic Electron Donors (OEDs) Enabled Radical Reactions

Over the past few decades, organic transformations facilitated by small organic molecules have witnessed considerable advancements. Small organic molecules have been widely applied to the construction of various skeletons. However, reduction as one of the fundamental reactions is generally initiated by metal‐containing reducing agents, although the initial progress of organic electron donors (OEDs) enabled reductive cleavage of some chemical bonds had been achieved in 1990s. Due to their structural diversity and tunability, OEDs can overcome the limitations of metal‐based reducing agents, such as low selectivity and poor functional group tolerance as well as the environmental problems caused by substantial inorganic waste after reactions. Building on a brief historical overview of OED research, this review focuses on the rencent advancements of the OEDs promoted radical reactions. It covers the reduction of C‐X (X =C, O, N etc.) single bonds, radical cyclization, intermolecular radical addition to unsaturated bonds, radical coupling, functionalization of aromatics, and C‐H bond activation. Additionally, the mechanistic insights of the typical reactions are highlighted for well understanding of the reaction mode involving OEDs.

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

AbstractHepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.

The Interconnection Between the Liver and Other Organs: Insights for Hepatic Long–Term Normothermic Machine Perfusion

ABSTRACTNormothermic machine perfusion (NMP) is emerging as a promising technique for organ preservation, evaluation, and scientific research, offering the potential to enhance the viability and function of donor organs. To fully harness the benefits of NMP, sustained long–term NMP (LNMP) at 36°C for periods exceeding 24 h is required. However, the development of stable LNMP devices is hindered by our limited understanding of ex vivo liver physiology. This review synthesizes insights from clinical and experimental studies to highlight the knowledge gaps associated with the impact of the absence of various organs or systems on isolated livers during ex vivo perfusion. Additionally, it discusses liver injuries and adverse events documented in published liver LNMP studies, elucidating their underlying mechanisms. By analyzing these findings, the paper proposes a series of recommendations to establish a more stable LNMP platform, aiming to optimize the outcomes of liver preservation and expand the applications of NMP in clinical practice and research.

​​Labile Bodies​: A Hospital Ethnography of Medical Professionals’ Struggles in Deceased Organ Donation

This article presents an ethnographic study of the donor body in deceased organ donation. Drawing on the science and technology studies’ incitement to study bodies being enacted and acted upon in situated practices, I explore the body being done and becoming undone in the practices of organ procurement at a Catalan hospital. The hospital has uniquely high rates of organ donation and transplantation, and deceased organ donation has become routinised and integrated into everyday hospital activities. I attend ethnographically to the medical professionals’ accounts of and interactions with bodies and organs in their work dealing with both donors after brain death diagnosis and uncontrolled donors after circulatory death diagnosis. During fieldwork, I followed the struggles of the transplant coordination team grappling with unruly bodies under different maintenance technologies. The body being done in these hospital practices is an active and unstable materiality that must be contended with: a labile body, or a fragile assemblage of interdependent functions, requiring multiple interventions provided by a host of dedicated hospital practitioners. The article shows that staying close to the medical professionals’ situated accounts is a valuable route to gaining novel understandings of the donor body.

Under pressure: Care, capacity and organ donation

In this paper, I seek to theorise the concept of pressure in relation to families’ experiences of organ donation during COVID-19. Drawing on Australia-based fieldwork, I follow circuitries of pressure in and beyond interiorities of bodies, biographies and infrastructures of care to ask what happens when pressure builds to such an extent that there is no capacity left in bodies and in institutions. Pressure concentrates in some spaces and bodies more than others revealing uneven flows and restrictions to care. But how might a theorisation of pressure enable care to be imagined otherwise – to circulate differently? Extending recent care scholarship, I explore alternative versions of care enacted by families and clinicians involved in organ donation. This is an expansive and capacious care, which may offer potential to diffuse the force of pressure through radical interdependence.

Promising Results of Kidney Transplantation From Donors Following Euthanasia During 10-Year Follow-Up: A Nationwide Cohort Study.

The outcome of kidneys transplanted following organ donation after euthanasia (ODE) remains unclear. This study analyzed all kidney transplantations in the Netherlands from January 2012 to December 2021, comparing the outcomes following ODE, donation after circulatory death (DCD-III), and donation after brain death (DBD). 9,208 kidney transplantations were performed: 148 ODE, 2118 DCD-III, and 1845 DBD. Initial graft function was compared between these categories. Immediate graft function, delayed graft function and primary non-function in ODE kidney recipients were 76%, 22%, and 2%, respectively, 47%, 50% and 3% in DCD-III kidney recipients and 73%, 25%, and 2% in DBD kidney recipients (overall p-value: p < 0.001). The number of kidneys transplanted over a median follow-up period of 4.0 years (IQR 2.0-6.6), was 1810, including 72 ODE, 958 DCD-III and 780 DBD kidneys. In this period, 213 grafts (11.8%) failed [7 grafts (9.7%) from ODE donors, 93 grafts (9.7%) from DCD-III donors, and 113 grafts (14.5%) from DBD donors]. Kidneys transplanted after euthanasia have a good immediate graft function, a comparable longitudinal 10years eGFR, and similar graft failure hazard to kidneys from DCD-III and DBD. Kidney transplantation following ODE is a valuable and safe contribution to the donor pool.

Dual hypothermic oxygenated machine perfusion of the liver reduces post transplant biliary complications - a retrospective cohort study.

Corroborating evidence for use of hypothermic oxygenated machine perfusion (HOPE) prior to orthotopic liver transplantation (OLT) suggests a beneficial effect in regards to biliary complications. Here, we aim to evaluate whether perfusion via portal vein alone (sHOPE) or via additional perfusion of the hepatic artery (dHOPE) have diverging impact on outcomes after OLT when compared to use of static cold storage (SCS). Consecutive patients undergoing OLT at Medical University of Vienna (2018 to 2023) were retrospectively analyzed. Donor organs were procured using SCS, or subjected to end-ischemic sHOPE or dHOPE. Severity of biliary complications was classified according to degree of therapeutic intervention (endoscopic retrograde cholangiopancreatography or surgical revision). 247 patients were included (69 SCS, 76 sHOPE, 102 dHOPE). Hospitalization was shorter for patients after HOPE (median in days: SCS=25 vs HOPE=20, P=0.019). Biliary complications were less frequent in patients after HOPE (SCS=37.7% vs HOPE=22.5%, P=0.015). A significantly lower incidence of surgical revisions for biliary complications was observed in the HOPE cohort (24.6% vs 11.8%, P=0.012). When evaluating outcome according to HOPE-modality, a significant reduction in biliary complications (P=0.006) and surgical revisions (P=0.002) was only observed in dHOPE patients in comparison to SCS. Further, only dHOPE was significantly associated with reduced need for surgical revision for biliary complications upon uni- and multivariable logistic regression (odds ratio=0.336, P=0.011). HOPE leads to a reduction of biliary complications and associated surgical revisions. This effect seems to be primarily associated with use of dHOPE, while both methods appear as feasible options for preconditioning of donor grafts prior to OLT.

Comparison of continuous flow centrifugal left ventricular assist devices as a bridge to transplant strategy in a low organ donation environment: single center experience

ObjectiveIn patients with advanced heart failure, heart transplantation is currently the most effective treatment. However, in a low-organ environment, it is usually necessary to proceed in long-term mechanical circulatory support through left ventricular assist device (LVAD) implantation as bridge-to-transplantation. MethodsThe study included all patients with advanced heart failure who underwent continuous flow LVAD implantation as a bridge to transplant strategy in our center (n = 68). Following LVAD implantation and for the period that patients were on LVAD support, pump thrombosis, strokes, gastrointestinal bleeding, and right heart failure occurrence rates were recorded. Outcomes were compared between patients implanted with HeartMate 3 (HM3) and HeartWare LVADs, as well as between patients who did reach heart transplantation (HTx group) and those who did not (noHTx group). ResultsA total of 35 out of 68 patients underwent heart transplantation at a mean time of 691 ± 457 days; 41 received a HeartWare and 27 a HM3 device. HM3 patients had significantly better survival (p = 0.010) and lower complication rates (p = 0.025). In addition, the noHTx group had significantly higher complication rates compared with the HTx group (p = 0.00041). The 5-year estimated Kaplan–Meier survival rate following heart transplantation was 77%. ConclusionPatients with advanced heart failure gain substantial benefit from LVADs awaiting heart transplantation. In a low organ donation environment, the need for reliable LVADs can further improve the outcomes through the reduction of complications provided by current devices.

Legal Framework for Security of Organ Transplant Information in the Digital Age with Biotechnology

In the context of the digital age, organ transplantation, as a life-saving technology, has become increasingly prominent in its information security. This paper aims to explore and construct a legal framework for organ transplant information security that meets the requirements of the digital age. First, the article outlines the legal background of organ transplantation and its new challenges in the digital age, emphasizing the centrality of information security in the organ transplantation process. The article then elaborates on the legal definitions and classifications of organs and discusses how digital technologies are changing these definitions and classifications. In the same way, the study of how people think about organ donation and transplantation used non-parametric tests, analysis of variance, and logistic regression to determine how people think about these things differently in different groups. Dichotomous logistic regression models were also created. This paper examines the current legal frameworks that protect organ transplant information in the digital age. The focus is on how biotechnology is linked to data privacy, security measures, and ethical concerns. This shows the importance of a complete regulatory framework to protect individuals' health information about organ transplants. This paper's research goal is to make a stronger legal guarantee for organ transplant information security. This will help organ transplantation technology grow healthily, protect the rights and interests of donors and recipients, and keep people's sense of dignity.