Initiated in 1967 by Professor Jon J. van Rood, the Eurotransplant International Foundation (Eurotransplant) is a non-profit organization coordinating the allocation of post-mortem donor organs in 8 European countries. Member countries of Eurotransplant are Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, Netherlands and Slovenia. Eurotransplant plays a central role in the just and efficient distribution of organs such as kidneys, livers, hearts, lungs, pancreases and intestines. ¹ Allocation is based on medical and ethical criteria [1, 2]. The most important criteria for organ allocation are blood group, donor size and age, tissue characteristics (HLA groups especially for kidneys), clinical urgency, waiting time, and regional availability (depending on organ type). ²

Three consent models exist for deceased organ donation. In Eurotransplant, Germany adopted the informed consent (opt-in) model, where the donor or their designated surrogate must explicitly confirm the donor’s willingness to donate before organ recovery. All other Eurotransplant countries apply an opt-out model based on presumed consent. Individuals are considered organ donors upon death unless they have registered an objection. ³ The third is the explicit authorization model, adopted in the United States, which requires explicit authorization from the donor emphasizing individual autonomy. ⁴ Each system reflects a different ethical and legal position on balancing personal choice with the need to maximize organ availability for transplantation.

The decision-making of organ suitability is guided by donor and recipient factors, transportation logistics, hospital and center policies, time of day, and, most importantly, the subjective assessment of the surgeons at the transplant centers. Notably, non-utilization rates increase during weekends and nighttime hours, highlighting the impact of human factors such as workload and decision fatigue [3, 4]. Hence, organ non-utilization is driven by subjective factors such as institutional risk aversion, labeling biases, and inconsistent interpretation of imperfect clinical data [5]. To reduce unnecessary organ non-utilization, it is crucial to establish more objective and standardized criteria.

Despite the efforts towards organ donation in the Eurotransplant region, the shortage of donor organs (1,424 waiting-list-deaths in 2024; ⁵ 140 million population ⁶ ) remains the key limiting factor in organ transplantation. Novel medical tools for organ preservation combined with the development of new technologies for assessment and treatment of donor organs [6, 7] enable for data-based organ quality assessment and higher organ utilization rates.

Normothermic machine perfusion (NMP) enables safe transplantation of high-risk donor livers that would otherwise not be utilized [8]. Normothermic regional perfusion (NRP) is used in donation after circulatory death (DCD) and has demonstrated higher utilization rates and better outcomes [9]. Machine perfusion has enabled functional assessment and recovery of marginal liver [10–18], kidney [19], pancreas and lung [20, 21] grafts. In pancreas transplantation, ex vivo NMP has been applied in an experimental setting and select centers to assess function in declined grafts [22, 23]. Ex situ organ perfusion platforms also serve to test perfusion solutions and additives under controlled conditions [24–26]. Broader use of perfusion technologies may help meet transplant demand [8, 27]. However, the challenge lies in deciphering the significance of this information to determine its most effective and efficient use in organ transplantation.

The accelerating pace of technological advancement has dramatically expanded the capacity to gather, analyze, and interpret data. Combined with artificial intelligence, machine learning, and biomedical imaging, this fuels the prospect of a more robust, data-driven and fair allocation system.

To bridge the widening gap between data acquisition and biological insight, it is imperative to obtain a greater number and diversity of human organs for research. The study of organs across different ages, ethnicities, disease states, and environmental backgrounds, may reveal meaningful biological signals with predictive value towards the outcome after transplantation. Therefore, expanding access to human organs, that otherwise would not be used is essential for fully realizing the potential of contemporary and future biomedical technologies.

The aim of this manuscript is to assess the current state of research on human organs deemed unsuitable for transplantation and to examine the legal framework and practical application across Eurotransplant. It highlights the need for improved policies and handling of these organs to expand research opportunities and increase organ availability.

Post-mortem organ donation remains a cornerstone of modern transplantation medicine, enabling life-saving treatments and improving quality of life. The public and academic discourse primarily focuses on successfully transplanted organs. Less attention is paid to organs recovered but ultimately deemed unsuitable for transplantation. It is important to emphasize from the outset that transplantation must remain the goal and overarching priority for every recovered organ. Any framework enabling research use of non-transplanted organs should only apply after all efforts towards transplantation have been exhausted. In case an organ is deemed non-transplantable, research addressing innovations that may foster to make currently non-transplantable organs transplantable in the future should be given priority over other research interests.

Non-transplanted organs hold considerable scientific value that remains largely untapped. Between 2014 and 2023, 332,072 and 32,242 organs were recovered but not utilized in the US and Eurotransplant, respectively. These numbers illustrate the huge potential in this field. Interestingly, organ utilization rates vary also by organ type. Abdominal organs (kidney, liver, and pancreas) tolerate longer cold ischemia times than thoracic organs and show heterogeneous acceptance rates. In contrast, thoracic organs (heart and lungs) have higher immediate functional requirements and limited ischemic tolerance, leading to more conservative donor selection and lower utilization [65–69]. The introduction of machine perfusion (NMP, HOPE, NRP) has mitigated some of these limitations by enabling functional assessment and extending preservation times ³² [9, 27].

A deceased donor organ may be unsuitable for transplantation yet transformative for research and development. Utilizing non-transplantable organs can support the development and validation of novel diagnostic tools, surgical techniques, and therapeutic approaches under conditions closely reflecting human physiology. Moreover, biomedical research often struggles to account for the variability in human populations, which limits the effectiveness of pre-clinical models. Studying human organs declined for transplantation offers a powerful alternative for assessment prior to clinical trials. Such organs allow for early assessment of viability and function. However, establishing the viability of such organs for transplantation remains inherently challenging. Unless the organ is ultimately transplanted and its function can be assessed in vivo, any conclusions remain speculative [27, 70]. While cell cultures and animal models remain valuable, their role should follow validation in human tissue. Once validated, animal models could then provide deeper mechanistic insights (or vice versa) [71]. Repurposing procured but not transplantable human organs for research directly aligns with 3R principle of Directive 2010/63/EU [72] by replacing less predictive animal models, reducing unnecessary animal use, and refining preclinical testing.

This manuscript covers three distinct categories of not transplantable organs: those deemed unsuitable before retrieval and therefore not even offered for transplantation, those offered for transplantation but not accepted by any transplant center, and those accepted for transplantation but excluded during the procurement or evaluation process and ultimately not used. Among these, particular attention should be given to organs that were initially accepted and procured but ultimately not transplanted (herein referred to as recovered organs). These organs represent a valuable resource because they have passed selection and logistical assessments and are already recovered. Therefore, future efforts in policy, ethics, and clinical practice should focus on this group, exploring safe and ethically sound ways to repurpose them for research, without compromising donor dignity or public trust. Utilizing organs that have already been recovered may also reduce dependence on animal testing. This is in line with broader ethical and scientific objectives.

Over the last 10 years, the number of non-transplanted organs within ET was stable. On average, 16.05% of all reported organs would qualify for potential secondary use under this framework. This consistency suggests a predictable source of organs for research. However, many Eurotransplant member countries lack a clear legal framework that governs the research use of organs not intended for transplantation. Current legislation is focused on transplantation, leaving little room for alternative, science-driven applications. This lack of regulation leads to uncertainty regarding research use. As a result, organs that could significantly advance medical knowledge are often disposed of.

What applies to non-transplanted organs also holds true for non-realized donors. The organs from these donors may hold considerable value. While the reasons for non-utilization of those donor organs are diverse and sometimes vague, the added value of using these organs for advancement and development in the field of transplantation and beyond needs to be considered. More, the conceptual link from unused organs to organ donors and further to whole-body donation for, e.g., anatomical education illustrates the close connection between these topics. At the same time, it reflects a broader societal attitude toward the idea of making one’s own body available for scientific purposes. This connection emphasizes not only the individual willingness to contribute to research but also society’s need to make use of such opportunities in order to advance medical knowledge and achieve improvements for the benefit of humanity.

The model of whole-body donation for research purposes is well established and widely accepted. Extending this framework to include individual organs that are not viable for transplantation appears ethically consistent. Such an extension would enhance scientific opportunities while respecting donor intent.

International comparisons highlight the feasibility of more inclusive policies. In the US research access to not transplantable donor organs is supported by both legal and institutional mechanisms, facilitating ethically sound and scientifically valuable work [73]. The number of reported donor organs differs considerably between the Eurotransplant region and the United States (735 pmp vs. 2,157 pmp respectively). Key factors influencing this discrepancy include the high donor rate resulting from the stronger incentivization system and the national guidance and coordination in the United States, the opioid crisis, as well as the low donor rate in Germany. Reasons why this system may capture a broader range of potential donors, including those whose organs are ultimately not used. While the incentive-based approach can be a strong driving force, it also exposes the system to scrutiny and demands strong objectivity in the decision-making process [74]. Hence, comparisons between reported donor numbers should be made with caution, as the underlying systems and reporting practices may differ. Anyway, these practices could serve as a point of reference for European countries seeking to modernize and refine their regulatory approaches.

An illustrative example from the United States is 34 Lives, a public benefit corporation dedicated to improving the utilization of viable donor kidneys at risk of not being utilized. 34 Lives employs advanced organ preservation strategies to sustain and, in some cases, restore kidney function. Preliminary data indicate that the initiative has led to higher transplantation rates, underscoring its potential to reduce organ wastage and improve outcomes for transplant recipients. ³²

Emerging technologies such as machine perfusion make it increasingly important to clarify access to non-transplanted human organs. In the liver, NMP has demonstrated feasibility for perfusion periods of up to 48 h, and even 7 days in some cases [75, 76], while maintaining key metabolic and structural functions. A human liver was perfused ex vivo for 3 days and subsequently transplanted, with the patient recovering normal liver function and quality of life without signs of rejection or bile duct injury after 1 year of follow-up [77]. Transcriptomic and metabolomic analyses during NMP have revealed activation of pro-survival and repair pathways in livers, along with effective autophagy and redox balance [78–80]. Composite viability criteria such as lactate clearance, pH, bile output, and vascular flow patterns have been successfully used to guide transplantation decisions [10, 12]. Long-term perfusion has also enabled metabolic interventions such as steatosis reduction [81, 82]. In addition, senolytic treatments applied during ex vivo liver perfusion have shown promise in preserving the regenerative capacity of the biliary system, by mitigating the detrimental effects of cellular senescence on cholangiocyte function and primary cilia integrity, which are crucial for biliary repair [83, 84]. In machine perfused human livers, adeno-associated virus (AAV) vectors were compared under neutralizing and non-neutralizing conditions, revealing distinct differences in transduction efficiency and antibody susceptibility [85]. Single-cell analyses further demonstrated that vector performance depends on liver condition and capsid choice [86]. Split-liver perfusion models enable direct intra-organ comparison of therapeutic interventions [87–89]. As a preclinical test, a liver from a patient with mitochondrial neurogastrointestinal encephalomyopathy was used to demonstrate AAV-mediated gene therapy in a human organ indicating feasibility of correcting the genetic defect [90].

In the kidney, 24- to 48-h normothermic perfusion with urine recirculation has shown stable flow and resistance, acid-base balance, and tissue morphology enabling functional assessment of organ condition [91–94]. Kidney NMP may eventually reduce non-transplantation rates and improve allocation [95, 96]. A study demonstrated that non-transplanted human kidneys can be preserved in a metabolically active and functionally stable state for up to 4 days using subnormothermic (25 °C) machine perfusion [97–99].

In the pancreas, NMP has been successfully applied in research settings to assess function in non-transplanted grafts. Stable perfusion, insulin secretion, and minimal histological injury was observed in preliminary studies [22, 23]. This approach remains investigational and is not currently part of routine clinical practice. Hypothermic perfusion also enables isolation of viable islets from DCD donor pancreases [100].

In lung transplantation, advances in machine perfusion have helped to preserve and treat organs. Techniques such as prone positioning may improve lower lobe function and reduce reperfusion injury [21]. Moreover, xenogeneic cross-circulation has demonstrated potential for the extracorporeal recovery of severely injured human lungs [20]. Some lungs initially deemed unsuitable were later found transplantable [21].

Beyond the immediate clinical use cases, ex situ organ perfusion facilitates decellularization of whole human livers and kidneys and generation of biological bioscaffolds [98, 99, 101]. In an attempt to generate bioengineered transplantable organs, these scaffolds have been reseeded with human cells. Delivery of multipotent adult progenitor cells during liver NMP resulted in transendothelial migration and secretion of immunomodulatory factors, demonstrating compatibility of cell therapy with perfusion platforms [102].

In conclusion, organs that have already been recovered but not transplanted should not be automatically excluded from further use. When guided by robust ethical standards and clear legal frameworks, their use in biomedical research represents an opportunity to advance science, possibly reduce animal testing, and ultimately benefit future patients. Achieving this will require public dialogue, political initiative, and a shift in perspective. Such an effort would also render organ donation more meaningful and, in the long term, more effective.