The scale of unmet need is staggering. In the United States, more than 103,000 patients sit on organ waiting lists and roughly 17 die each day before a suitable graft arrives. Europe performs around 34,000 transplants annually while approximately 60,000 patients wait. The gap widens dramatically in emerging economies: China performs some 20,000 to 25,000 transplants a year against a deceased-donor rate below four per million population, while India carries out only about 13,500 kidney transplants for roughly 100,000 patients who need one each year. Pigs, with their physiological similarity to humans, short gestation times, large litters, and amenability to genome editing, are the leading candidate to close this gap, but only if production can be scaled to match demand.

Modern donor pigs are biological platforms of remarkable complexity. The leading animals carry knockouts of the GGTA1, CMAH, and B4GALNT2 genes, which eliminate the major xenoantigens αGal, Neu5Gc, and Sd(a) that trigger hyperacute rejection, plus additional human transgenes that temper immune and coagulation incompatibilities. The donor pig used in the first clinical heart xenotransplantation carried ten genetic modifications. Producing such animals at clinical scale relies on somatic cell nuclear transfer, embryo transfer, artificial insemination, and cryopreservation, all while maintaining precise genotypes and strict microbiological standards. The authors model output with a formula combining litters per sow, live-born piglets, pre-weaning and production survival, the proportion retaining designated pathogen-free qualification, and the proportion meeting genetic and organ-specific donor criteria, a reminder that herd mathematics, not just molecular biology, will determine whether organs reach patients.

The arithmetic is sobering. Assuming two transplantable kidneys per pig, Europe would need a theoretical minimum of 10,000 to 12,500 donor pigs annually just to replace current kidney transplant activity, and realistic estimates that account for donor exclusion, organ discard, transport losses, and reserve capacity push the figure to 15,000 to 20,000. The United States would require roughly 18,000 to 20,000. Asia dwarfs both: meeting even a fraction of projected kidney demand in China could require 75,000 to 150,000 donor pigs a year, with India needing 50,000 to 75,000. A facility producing 5,000 clinically eligible donor pigs annually would need around 250 to 300 breeding sows and a total herd of 3,000 to 5,000 animals. Replacing Germany’s kidney transplant activity alone would demand one dedicated large-scale facility; Europe or the United States would likely need three to five production centers.

Biosafety forms the second pillar of the logistics challenge. Donor pigs must be raised in designated pathogen-free facilities operating like high-containment biomedical production plants, with positive-pressure barrier housing, HEPA-filtered ventilation, sterilized feed and water, restricted personnel access, and continuous environmental monitoring. The DPF pathogen panel is defined by intended clinical use rather than a fixed list, and surveillance targets porcine cytomegalovirus, porcine reproductive and respiratory syndrome virus, hepatitis E virus, circoviruses, influenza viruses, and porcine endogenous retroviruses. The stakes were made vivid by the first clinical pig-heart transplant, in which PCMV was detected in the donor organ and likely contributed to graft dysfunction; preclinical studies in non-human primates show the virus markedly shortens xenograft survival. Porcine endogenous retroviruses pose a distinct problem because they are woven into the pig genome, though CRISPR-Cas9 approaches have now inactivated multiple PERV sequences in donor animals, and no clinical transmission has ever been documented.

The review also stresses reverse logistics, an aspect rarely discussed. Biosecure networks need predefined procedures for isolating animals after suspected pathogen exposure, movement restrictions during outbreaks, safe disposal of culled donor animals, and validated containment and decontamination pathways for biological samples and medical waste. Recipients themselves become part of the surveillance architecture: regulators in both the United States and Europe recommend lifelong monitoring, periodic virological screening, donor tissue archiving, and participation in national registries. Every xenograft must be traceable back to its donor animal, breeding facility, genetic background, and screening results, documentation that resembles pharmaceutical batch records more than transplant charts. Paradoxically, the authors note that because viruses such as HIV-1, human cytomegalovirus, Epstein-Barr virus, and even rabies have been transmitted through human allotransplants, carefully screened xenotransplantation may ultimately prove safer on infectious-disease grounds than conventional transplantation.

The most transformative lever, however, may be machine perfusion. Static cold storage imposes hard limits: hearts tolerate only four to six hours of cold ischemia, lungs six to eight, livers eight to twelve, and kidneys 24 to 36. Hypothermic oxygenated perfusion keeps organs at low metabolic demand while delivering controlled oxygen, supporting mitochondrial recovery, and clinical studies in kidney transplantation show reduced delayed graft function. Normothermic machine perfusion goes further, keeping organs metabolically active so that vascular resistance, oxygen consumption, urine production, and bile secretion can be monitored in real time, turning preservation from passive storage into active quality assessment. Preservation periods exceeding 24 hours have already been reported for several organ types, and experimental work has successfully perfused gene-modified porcine kidneys, livers, and lungs on clinically approved systems. Extended windows could let centrally produced organs be distributed across entire countries or continents.

Distribution architecture is the final piece. Centralized mega-facilities offer standardized quality control and economies of scale but create single points of failure and long transport routes. Fully decentralized facilities near transplant centers shorten distances but duplicate expensive infrastructure and surveillance systems. The authors favor a hybrid regional hub-and-spoke model, in which strategically located donor facilities supply perfusion hubs that assess, optimize, and redistribute organs, a concept already demonstrated by collaborative perfusion hubs evaluating αGal-knockout porcine livers and lungs under normothermic conditions. Europe’s existing cross-border infrastructure, notably Eurotransplant, could provide the framework for such networks. Asia faces different constraints, including vast distances, uneven cold-chain and air-cargo capacity, and heterogeneous national regulations, which may favor regionally clustered production rather than centralized megafacilities.

Economics and public acceptance will shape demand as much as medical need. Dialysis costs frequently exceed 60,000 to 100,000 euros per patient annually in Europe and around 90,000 dollars in the United States, and registry analyses show kidney transplantation becomes cheaper than dialysis within roughly three years, making scalable xenotransplantation potentially cost-saving for chronic kidney disease. Yet the acquisition cost of a gene-edited pig organ remains essentially unquantifiable until production reaches clinical scale, and early procedures will be expensive. A survey in China found that although most respondents had heard of xenotransplantation, only 4.9 percent considered themselves very familiar with it and just 36.7 percent would definitely accept a life-saving xenograft, with concerns centering on safety, outcomes, and cost. Looking further ahead, advances in vitrification and nanowarming have enabled rat kidneys to be cryopreserved for up to 100 days and successfully transplanted, and liter-scale vitrification has been demonstrated in porcine livers, hinting at future organ banks that would fully decouple procurement from surgery. If the supply chain the authors envision can be built, transplantation could evolve from a scarcity-driven emergency discipline into a predictable, scalable therapeutic platform, one planned pig herd, perfusion hub, and delivery route at a time.

Subject of Research: Logistics and supply-chain requirements for clinical pig-to-human xenotransplantation

Article Title: Logistics of clinical xenotransplantation: from donor pig production to global organ distribution

Article References: Fischer, K., Denner, J., Tönjes, R. R., Felgendreff, P., & Rahmel, A. (2026). Logistics of clinical xenotransplantation: from donor pig production to global organ distribution. Transplant International, 39, Article 17326. https://doi.org/10.3389/ti.2026.17326

Image Credits: AI Generated

DOI: 10.3389/ti.2026.17326

Keywords: xenotransplantation, donor pigs, gene editing, organ shortage, machine perfusion, biosafety, organ preservation, organ distribution, porcine endogenous retrovirus, regulation, dialysis costs, public acceptance

The review, authored by Rachana Yogesh Patil of Pimpri Chinchwad College of Engineering and Yogesh H. Patil of D. Y. Patil College of Engineering in Pune, India, takes a deliberately broad view. Rather than examining artificial intelligence, blockchain, organ preservation or digital health in isolation, as most previous reviews have done, it synthesizes these emerging technologies with global transplantation trends, donor utilization patterns and implementation barriers within a single framework. The authors conducted a structured literature search across five electronic databases, screening 512 records down to 69 studies for qualitative synthesis, with a focus on publications from 2020 to 2026. Their conclusion is blunt: transplantation systems remain disjointed, and the missing integration of infrastructure, policy and technology is now as much of a problem as the shortage of donors itself.

The data the authors compiled reveal how uneven the global picture really is. According to the Global Observatory on Donation and Transplantation, 173,727 solid organ transplants were reported across 92 countries in 2024. Kidney transplants dominated with 110,467 procedures, roughly 64 percent of the total, followed by liver transplants at 42,497, or about 24 percent. Heart transplants accounted for 10,287 cases and lung transplants for 8,236, while pancreas transplants numbered just 2,066 and small bowel transplants a mere 174. When the authors normalized these figures per million population, the regional disparities became dramatic. The Americas led with 69.96 transplants per million people and Europe followed at 63.28, but South-East Asia managed only 12.09 and the Eastern Mediterranean 11.51. Africa recorded just 1.35 transplants per million people, a figure the review describes as a serious concern for access, infrastructure and resources.

Donor utilization efficiency, the capacity to convert identified donors into successfully transplanted organs, emerged as one of the most telling performance indicators in the analysis. Between 2014 and 2024, overall deceased donor utilization rates climbed steadily from 89.77 percent to 94.20 percent. Donation after brain death proved the most efficient donor type, rising from 88.74 percent to 96.76 percent, a trend the authors attribute to well-developed clinical guidelines, improved organ viability and streamlined decision-making. Donation after circulatory death told a very different story. Utilization rates fluctuated sharply, dropping to 45.23 percent in 2018 before recovering and stabilizing at around 87.88 percent in recent years. The review notes that the reasons for the 2018 decline cannot be determined from aggregated data and may reflect changes in reporting practices, donor selection criteria or allocation policies, but the persistent gap between brain-death and circulatory-death donors points to structural inefficiencies, including warm ischemia that degrades organ quality after circulatory arrest.

The imbalance extends to the donor sources themselves. Kidney transplantation drew on both pools in 2024, with 69,472 organs from deceased donors and 40,995 from living donors, while liver transplants combined 32,618 deceased-donor and 9,865 living-donor cases. Thoracic organs, by contrast, rely almost entirely on deceased donors, since hearts and lungs cannot be partially donated and tolerate only very short preservation windows. Living donors provide roughly 37 percent of kidney and 23 percent of liver transplants globally, which the review frames as both a strength and a warning sign. Healthy people undergo major surgery with no direct medical benefit, exposing them to surgical risks, long-term health effects and psychological pressure. The authors argue that heavy reliance on living donation also signals that deceased donor programs are under-optimized, and that differences in the availability of willing donors can create inequities in transplant access tied to social, family and economic backgrounds.

Logistics and preservation constraints compound these problems. Organ transplantation is a race against cold ischemia time, the period during which an organ is deprived of blood flow at low temperature before graft failure risk climbs. Hearts and lungs must be transplanted within a few hours, while kidneys have a longer shelf life, placing enormous pressure on coordination among donor hospitals, procurement organizations, transport systems and transplant centers. Any communication failure can lead to organ discard, especially in geographically dispersed systems. Donation after circulatory death is particularly vulnerable because organs are exposed to ischemic damage before retrieval. Static cold storage remains the cheapest and most widely used preservation method, but its shortcomings are increasingly apparent for marginal organs, and machine perfusion technologies, though clinically proven, are not yet universal because of cost and infrastructure requirements.

Against this backdrop, the review examines the technologies that could transform the field. Artificial intelligence applications fall into four domains: donor-recipient matching, organ offer and discard prediction, post-transplant outcome prediction, and allocation policy simulation. The evidence is nuanced. Externally validated models such as the D-TOP kidney transplant outcome prediction tool have outperformed traditional indices, and deep learning approaches have achieved roughly 98 percent matching accuracy in kidney matching prototypes and about 10 percent improvement in kidney discard prediction. Yet other studies found machine learning performed only similarly to regression-based methods, and most research remains retrospective, registry-based or single-center, lacking the prospective external validation needed to establish generalizability. The authors conclude that AI should be viewed as a decision-support technology that augments, rather than replaces, clinician judgment, with challenges including algorithmic bias, data drift and interpretability.

Blockchain, meanwhile, is positioned as coordinating infrastructure rather than a standalone solution. Decentralized, tamper-resistant ledgers combining smart contracts, decentralized registries and permissioned access control could secure donor registration, waiting list integrity, consent traceability, organ custody tracking and audit logging. Sensitive clinical data would be stored off-chain, with the blockchain holding hashes and transaction histories to preserve privacy. Blockchain paired with Internet of Medical Things sensors could monitor organ transport conditions and custody chains in real time, increasing accountability and reducing mishandling risks. But most blockchain applications remain at the prototype or pilot stage, built on platforms such as Ethereum and Hyperledger Fabric, and the review stresses that blockchain does not address organ shortage, allocation fairness or clinical decision complexity, which depend on policy and institutional practice. IoMT itself faces barriers of data security, device reliability, network dependency and integration with hospital information systems.

Organ preservation is where the review finds the greatest clinical maturity. Hypothermic machine perfusion reduces metabolic demand while maintaining cellular integrity, proving especially useful for high-risk kidney and liver grafts, while normothermic machine perfusion restores near-physiological conditions and allows real-time functional assessment and even repair of organs before transplantation. Emerging sequential perfusion combines the protection of hypothermia with the evaluation capabilities of normothermia. More experimental approaches push the frontier further: supercooling preserves livers at subzero temperatures without ice formation, partial freezing has enabled ten-day storage of rat livers in preclinical work, and vitrification with nanowarming offers ice-free cryogenic preservation with rapid, uniform rewarming that could eventually enable true long-term organ banking, though cryoprotectant toxicity and scalability remain obstacles. Big data analytics and clinical decision support systems round out the ecosystem, combining electronic health records, donor registries and real-time monitoring data to forecast organ supply and demand and support evidence-based allocation, though data heterogeneity, quality and privacy issues persist.

The review’s future directions converge on integration rather than invention. The authors call for interoperable data ecosystems with standardized data models and secure cross-institutional sharing protocols, explainable and equitable AI frameworks, scalable and cost-effective preservation technologies, and translational research in tissue engineering and bioartificial organs that could reduce dependence on donor organs. Equally important, they argue, is tackling the infrastructure gap between high-income and low- and middle-income regions through capacity building, international cooperation and affordable solutions for resource-poor settings. The vision is a data-driven, patient-centered transplantation system in which intelligent forecasting, secure data exchange and real-time monitoring work together. Success, the authors conclude, will depend not on any single technology but on matching digital innovation with clinical workflows, policy support, ethical governance and sustained international collaboration to make transplantation efficient, transparent and accessible on a global scale.

Subject of Research: Emerging technologies and systemic challenges in organ donation and transplantation systems

Article Title: Transforming organ donation and transplantation: challenges, innovations, and future directions

Article References: Patil, R. Y., & Patil, Y. H. (2026). Transforming organ donation and transplantation: challenges, innovations, and future directions. Frontiers in Transplantation, 5, Article 1855853. https://doi.org/10.3389/frtra.2026.1855853

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.1855853

Keywords: organ transplantation, organ donation, artificial intelligence, blockchain, Internet of Medical Things, machine perfusion, organ preservation, big data analytics, donor shortage, health equity, allocation policy, transplant logistics

Singapore’s selection as host was substantively apt. The city-state’s transplant programme exemplifies both the achievements and the persistent strains of the Asia-Pacific region: technical excellence spanning deceased and living donor liver transplantation, ABO-incompatible transplantation and increasingly minimally invasive donor surgery, all within a healthcare system confronting an organ shortage common across the region. More than 400 patients remain on Singapore’s national waiting list, with the liver among the most needed organs—a statistic that grounded the congress’s scientific ambition in immediate clinical urgency. In a symbolic tribute, a new orchid hybrid, Vanda Hepatica Nova (Latin for “new liver”), was launched in honour of the meeting, while the legacy “Tree of Life” planting project at Singapore hospitals commemorated organ donors and their families.

The dominant surgical narrative of the congress was robotic donor hepatectomy (RDH), which appears to be moving decisively from pioneering technique toward emerging clinical standard. The LDLTregistry.org Collaborative analysed 2,600 donors at 62 centres and found that RDH achieved the lowest blood loss, the shortest hospital stay and the lowest major complication rate—0.3 percent—compared with 3.7 percent for laparoscopic and 1.9 percent for open approaches. A single-centre analysis of 339 living left-lobe donors reported significantly lower blood loss with RDH (77 versus 316 millilitres) and a lower recipient morbidity rate of 40 percent versus 59 percent. The A2ROBOT study confirmed safety across 88 robotic donor hepatectomies at four US centres, with 5.7 percent major morbidity and no donor mortality.

Risk stratification featured prominently alongside these headline results. Portal vein complications, which occur in roughly 1.9 percent of right-lobe hepatectomies, were predicted by a main-to-left portal vein angle below 60 degrees, variant anatomy, absent falciform fixation and a body mass index above 30. Intraoperative hepatic artery flow below 55 millilitres per minute was strongly associated with small-for-size syndrome, while the FLAME model achieved an area under the curve of 0.81 for predicting early graft failure using four postoperative markers. In an open-label randomised trial of donor regeneration, ursodeoxycholic acid supplementation was found to enhance liver growth velocity by day 14 in right-lobe donors. Minimally invasive transplantation is also extending to recipients: laparoscopic-assisted liver transplantation in 15 patients with hepatocellular carcinoma and severe portal hypertension required no transfusion, and robotic recipient transplantation showed decreased blood loss, fewer infections, shorter intensive care and hospital stays, and 100 percent graft and patient survival at three months.

Machine perfusion emerged as perhaps the most forward-looking theme of the meeting, with normothermic machine perfusion reframed from a preservation tool into an active therapeutic platform. Perfusate flavin mononucleotide (FMN) stood out as a landmark biomarker: De Goeij and colleagues demonstrated that FMN during abdominal normothermic regional perfusion predicted biliary complications with an AUROC of 0.799 in perfusate and 0.732 in bile, while Cleveland Clinic data from more than 1,700 NMP samples validated FMN’s predictive power with an AUROC of 0.94 over the first four hours. Prospective FMN assessment was independently associated with a 44 percent reduction in the 90-day comprehensive complication index. Al-Adra and colleagues applied spatial transcriptomics to donation-after-circulatory-death livers before and after NMP, identifying NF-κB/IL-10 downregulation as a protective signature against ischaemic cholangiopathy, and the Royal Prince Alfred group reported the first transcriptomic analysis of human livers maintained for up to three weeks on long-term NMP, showing functional recovery, stable metabolism and preserved histology. Experts cautioned, however, that severe macrovesicular steatosis exceeding 30 percent remains problematic even after perfusion.

Artificial intelligence is no longer aspirational in this field—it is in clinical use and being rigorously evaluated across every stage of the transplant pathway. Explainable machine learning using LightGBM with SHAP achieved superior discrimination for short-term waitlist mortality compared with MELD, MELD-Na and MELD 3.0, highlighting functional status, bilirubin kinetics and ascites severity as novel predictors. Automated nnU-Net segmentation showed strong accuracy for hepatocellular carcinoma lesions larger than two centimetres, deep-learning intraoperative navigation demonstrated feasibility for real-time avascular-plane segmentation in minimally invasive donor surgery, and an LLM called HCC-LT-ProBot predicted HCC recurrence with high accuracy by integrating literature knowledge with multi-institutional datasets. Smartphone photograph recognition classified donor steatosis at 85 to 90 percent accuracy, and AI auto-segmentation reduced expert operative video review time roughly one hundredfold. In a State-of-the-Art lecture, Professor Dean Ho of the National University of Singapore framed AI as “augmented intelligence”—an adjunct that enhances clinical judgement rather than replacing it—insisting that prospective multi-centre validation remains the essential next step.

Transplant oncology continued to expand its boundaries. Global leaders discussed liver transplantation techniques applied to advanced perihilar cholangiocarcinoma, the RAPIDE procedure for biliary malignancies and ex situ resection of colorectal liver metastases, while Dr Olivier Scatton reviewed transplantation as a gold standard for rare hepatic malignancies, with excellent outcomes in neuroendocrine tumours and hepatic adenomas but poorer results in fibrolamellar carcinoma and sarcomas. Serial circulating tumour DNA testing was shown to effectively identify early HCC recurrence after resection and transplantation. Notably, French national data from 7,981 recipients demonstrated that everolimus exerted a protective effect against de novo malignancies, and the ETELITH study showed that everolimus significantly reduced HCC recurrence within the first five years after transplantation while improving overall survival.

The congress also marked a qualitative shift in xenotransplantation. Building on Tao and colleagues’ 2025 Nature report of gene-modified pig-to-human liver xenotransplantation, Shaked and colleagues demonstrated the feasibility of genetically modified porcine livers as a bridge to transplantation in a brain-dead human decedent model, achieving haemodynamic stability, metabolic function, modulated immune activation and reduced hyperacute rejection. The emerging consensus is that porcine livers as a bridging device, rather than a definitive transplant, represent the most near-term achievable clinical application, pending regulatory pathway development. Complementing this, van der Laan’s group developed macrophage-augmented organoids from pluripotent stem cells, yielding insights into hepatitis E virus replication and SARS-CoV-2 biology, while spatial transcriptomics in paediatric acute liver failure linked impaired T-cell exhaustion and macrophage polarisation to reduced liver regeneration.

Paediatric milestones drew particular attention, including Professor Mohamed Rela’s world-first robotic auxiliary partial orthotopic liver transplantation in a seven-year-old child with a urea cycle defect, which demonstrated precision, faster recovery, reduced scarring and minimised psychological impact. A systematic review of ABO-incompatible paediatric liver transplantation in the rituximab era reported one-year graft survival of 99.3 percent and patient survival of 97 percent, and ROTEM-guided transfusion significantly reduced blood product use. In transplant hepatology, the Toronto group showed that early living donor transplantation for alcohol-associated liver failure without a strict six-month abstinence rule achieves low relapse of 12 percent with no graft loss attributable to alcohol at five years when multidisciplinary evaluation is enforced, while GLP-1 receptor agonists, THR agonists and FGF-21 analogues represent emerging options for MASH, a growing waitlist contributor with roughly 20 percent post-transplant prevalence.

A recurring counterweight throughout the congress was the economics of innovation. The Business Practice Symposium underscored the high costs of combined perfusion strategies, calling for simplification, training and global pricing models to expand access; weighed the startup costs of robotic programmes against long-term efficiencies; and urged that AI undergo prospective validation before deployment at scale. For the Asia-Pacific region, where living donor liver transplantation volumes are the largest globally, HDI-stratified disparities in donor safety, heterogeneous regulatory frameworks for deceased donation and donation after circulatory death, and financial barriers to advanced technologies remain enduring challenges that no single institution can solve alone. The congress’s meta-narrative, Kow concludes, is convergence: robotics, machine perfusion, artificial intelligence and molecular science are no longer isolated innovations but intersecting forces—AI guides robotic navigation, perfusion provides the substrate for biomarker discovery, and organoid models illuminate the immunology that AI tools attempt to predict—leaving the field with a productive scepticism that welcomes transformative technology while demanding sustainable, equitable implementation.

Subject of Research: Emerging research and clinical perspectives in liver transplantation presented at the 30th ILTS Annual Congress 2025 in Singapore

Article Title: Reflections on liver transplantation: emerging research and clinical perspectives in 2025

Article References: Kow, A. W.-C. (2026). Reflections on liver transplantation: emerging research and clinical perspectives in 2025. Frontiers in Transplantation, 5, Article 1923144. https://doi.org/10.3389/frtra.2026.1923144

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.1923144

Keywords: liver transplantation, robotic surgery, machine perfusion, artificial intelligence, xenotransplantation, ILTS 2025, transplant oncology, organ donation, Reflections, liver, transplantation, emerging

VCA differs fundamentally from solid organ transplantation. Instead of replacing a heart or kidney, surgeons transfer composite tissues such as skin, muscle, bone, vessels, and nerves to restore structures like hands, faces, abdominal walls, uteri, and genitourinary organs. Contemporary procedures aim not only to rebuild anatomy and physical function but also to improve what clinicians call embodiment, identity, dignity, autonomy, and social participation in patients who have suffered devastating tissue loss. That ambition, however, comes with a distinctive ethical tension. Unlike a heart transplant, most VCA procedures are life enhancing rather than life saving, which forces clinicians to weigh functional benefit against the lifelong risks of immunosuppressive therapy, including infection, malignancy, and metabolic disease.

The special issue opens with a historical lens. A bibliometric analysis by Njessi and colleagues examined the one hundred most cited publications in the field and traced how the scientific literature has been shaped by hand and face transplantation, immunological innovation, rehabilitation science, and ethical discourse. The analysis underscores just how interdisciplinary contemporary VCA research has become, with no single specialty able to claim ownership of the field’s progress. It also provides a useful benchmark for measuring which areas, such as tolerance induction and digital monitoring, are now generating momentum and which remain underexplored.

Technological innovation features prominently throughout the collection. A systematic review by Chakradhar and colleagues synthesizes emerging technologies in immunomodulation, targeted drug delivery, tolerance induction, machine perfusion, biomarkers, and digital innovation. Among the most promising approaches are localized tacrolimus delivery systems that concentrate immunosuppressive drug action at the graft itself, hydrogel based immunosuppressive platforms that release medication gradually, mesenchymal stem cell therapies that may recalibrate the immune response, and mixed chimerism protocols designed to persuade the recipient’s immune system to accept donor tissue as self. The overarching goal is to reduce the burden of lifelong systemic immunosuppression while improving graft survival and enabling genuinely individualized care, a combination that would fundamentally alter the risk-benefit calculus for prospective recipients.

One of the most striking translational contributions comes from Duru and colleagues, who demonstrated successful twenty four hour ex vivo perfusion of vascularized composite allografts in a large animal limb model. Prolonged extracorporeal preservation of this kind could transform donor logistics across the field. Currently, the viability window for composite tissue grafts is short, which constrains how far donor organs can travel, how thoroughly donor and recipient can be matched, and how much time surgical teams have to plan complex multi-team operations. If extended preservation proves safe in humans, it could mitigate ischemia reperfusion injury, broaden geographic allocation, and ultimately widen access to VCA for patients far from the handful of centers currently performing these procedures.

The issue also reaches into specialized domains of transplantation medicine. D’Elia and colleagues reviewed immunosuppressive management in uterine VCA and pregnancy, a setting with unique challenges. Uterine grafts are temporary by design, intended to be removed after successful childbirth, and the immunological relationship between mother and fetus adds a second layer of complexity. Pregnancy itself alters the pharmacokinetics of immunosuppressive drugs, meaning that blood levels can shift unpredictably across trimesters. The authors emphasize the need for individualized therapeutic monitoring, pregnancy compatible immunosuppressive agents, and future development of noninvasive rejection monitoring and tolerance inducing approaches that could protect both mother and developing child.

Yet the collection’s central message is that technology alone cannot define success. Kumnig’s own mini review argues for a biopsychosocial technological framework that integrates biomedical advances with psychosocial care, ethical reflection, and patient centered research. Meaningful outcome assessment in VCA, the review contends, must extend well beyond graft survival and technical outcomes to incorporate quality of life, psychosocial resilience, rehabilitation adherence, informed decision making, embodiment, and social reintegration. This reframing matters because a technically perfect hand graft that the recipient neglects in rehabilitation, or a facial graft that fails to restore social confidence, represents a very different kind of outcome than the surgical record alone would suggest.

Psychosocial evaluation receives detailed attention. Antas and Nyberg, drawing on the Finnish experience with VCA, describe psychosocial suitability as a dynamic and multidimensional construct that extends far beyond the simple absence of psychiatric illness. Their work highlights psychosocial functioning, cognitive capacity, social context, and mentalization capacity, which is the ability to understand one’s own and others’ mental states, as particularly important dimensions for preoperative evaluation and long term follow up. Because VCA recipients must adhere to complex medication regimens, attend frequent monitoring appointments, and engage in years of rehabilitation, the assessment of suitability is not a one-time gatekeeping exercise but a continuous process that evolves with the patient’s circumstances.

Ethical and developmental questions come into sharpest focus in a contribution by McKenna and colleagues on facial transplantation in emerging adulthood. Individuals between eighteen and twenty five years of age occupy a unique position in the VCA landscape. On one hand, they may be among the patients who stand to benefit most, since restoring a face at a life stage dominated by identity formation and social integration could yield profound improvements in personal development and participation. On the other hand, ongoing cognitive development in this age group may complicate informed consent, treatment adherence, and long term decision making. The authors advocate for developmentally tailored psychosocial support strategies specifically designed for this vulnerable yet potentially highly benefiting population, a recommendation that could influence patient selection protocols at VCA centers worldwide.

Taken together, the contributions offer a roadmap for the coming decades of VCA research and clinical implementation. The editors and authors converge on several structural priorities: harmonized international registries to pool outcomes across centers, standardized psychosocial outcome measures so that results from different programs can be compared, long term follow up protocols that track recipients for decades rather than years, and ethically grounded frameworks for patient selection and informed consent. Advances in immunomodulation, machine perfusion, digital technologies, and regenerative approaches continue to expand what is surgically possible, but the field’s own analysis suggests that sustainable progress depends equally on patient centered care, equitable access, and the capacity to support the complex psychological, social, and ethical realities that recipients navigate throughout their lifelong transplantation journey. As VCA moves from experimental achievement toward established clinical practice, the measure of its success will increasingly be written in the quality of recipients’ lives rather than in the record books of surgical firsts.

Subject of Research: Vascularized composite allotransplantation research and interdisciplinary clinical evolution

Article Title: Editorial: How current and future approaches and research results contribute to evolve the field of vascularized composite allotransplantation

Article References: Kumnig, M. (2026). Editorial: How current and future approaches and research results contribute to evolve the field of vascularized composite allotransplantation. Frontiers in Transplantation, 5, Article 1993324. https://doi.org/10.3389/frtra.2026.1993324

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.1993324

Keywords: vascularized composite allotransplantation, hand transplantation, face transplantation, immunosuppression, machine perfusion, psychosocial assessment, tissue grafts, medical ethics, rehabilitation medicine, transplantation immunology, patient-centered medicine, Editorial

The editorial collection, assembled by Aleah L. Brubaker and Gabriel T. Schnickel of the University of California San Diego, frames the central shift of the past decade: clinicians are no longer merely preserving donated organs but resuscitating them, probing their function, and modifying their biology before implantation. Three main techniques anchor this transformation. Hypothermic machine perfusion (HMP) pumps chilled, oxygenated solution through the organ at low temperatures, reducing ischemic injury while allowing continuous delivery of protective agents. Normothermic machine perfusion (NMP) keeps the organ at body temperature with oxygenated blood or blood substitutes, sustaining near-physiologic metabolism so that bile production, lactate clearance, and other real-time markers can be measured. Normothermic regional perfusion (NRP) operates inside the donor, restoring circulation to the abdominal organs after circulatory death while excluding the brain, a strategy that has dramatically expanded the pool of usable organs from donation after circulatory death.

A comprehensive review by Olaso and colleagues lays out the landscape across liver, kidney, pancreas, and intestinal transplantation, and its most important contribution may be its honesty about what the field does not yet know. Machine perfusion clearly offers opportunities for viability assessment, greater use of marginal grafts from older or steatotic donors, and therapeutic intervention during the perfusion interval itself. But the review emphasizes that the technology faces shared obstacles across all abdominal organs: high cost, logistical complexity, lack of standardized protocols, and unresolved questions about which organs and which clinical circumstances actually benefit. A steatotic liver teetering on the edge of usability may gain enormously from hours of normothermic perfusion and metabolic conditioning, while a pristine kidney from a young donor may derive little advantage that justifies the expense and infrastructure. Defining those boundaries is now a central research priority.

The most dramatic illustration of how perfusion is rewriting the rules of organ recovery comes from Assouline and colleagues, who describe a case in which surgeons converted from veno-arterial extracorporeal membrane oxygenation to abdominal NRP after extracorporeal cardiopulmonary resuscitation failed in a patient with a Stanford type A aortic dissection, one of the most catastrophic cardiovascular emergencies in medicine. Despite the extraordinary complexity of the scenario, abdominal NRP enabled successful organ recovery and transplantation, demonstrating how innovative preservation techniques can create donation opportunities that would have been impossible under traditional protocols. The case underscores a broader point: NRP is not simply a preservation tool but a recovery strategy that changes which donors the system can serve.

Yet NRP remains the most ethically contested technology in the field. Because the technique restores circulation after the declaration of death by circulatory criteria, critics and some health systems question whether regional reperfusion constitutes a violation of the dead donor rule, and rigorous safeguards are required to prevent any cerebral reperfusion. Some countries and health systems do not currently permit NRP recovery at all. The editorial authors argue that as adoption expands, transparency, continued engagement with clinicians, ethicists, donor families, and the public, and unambiguous safeguards against brain reperfusion will remain essential. The technology’s clinical promise cannot be separated from the social license that permits its use, and that license must be earned case by case, system by system.

Beyond rescue and assessment, machine perfusion is opening a genuinely new therapeutic frontier: using the perfusate itself as a drug delivery vehicle. Mayoral and colleagues reviewed the pharmacologic supplementation of hypothermic kidney preservation and identified a substantial body of preclinical work targeting the molecular pathways of ischemia-reperfusion injury, the cascade of oxidative and inflammatory damage that occurs when an organ is deprived of blood and then reoxygenated. Clinical translation remains limited, but the conceptual shift is profound. Preservation solutions and perfusates, once inert fluids, are becoming platforms for targeted therapy, allowing drugs, gene therapies, or metabolic modulators to be delivered directly to an organ in a controlled circuit, away from the systemic exposure and side effects that complicate treatment in a living patient.

Tropp and colleagues extend this logic to the ultimate therapeutic ambition: regeneration. Their review maps the complex cellular and molecular networks that govern hepatic regeneration and proposes ex vivo machine perfusion as a bridge between mechanistic biology and clinical transplantation. Because perfusion maintains whole-organ architecture in a controlled environment, regenerative pathways can be measured, manipulated, and augmented before the organ ever reaches a recipient. In this framework, the goal moves beyond preserving the organ that was donated toward improving the organ that will ultimately be transplanted, a distinction that could eventually allow marginal livers to be conditioned into high-quality grafts rather than discarded.

Technological transformation, the collection stresses, cannot occur independently of the people who deliver it. Mullens and colleagues examine machine perfusion from the perspective of the next generation of transplant surgeons, and their analysis reveals a double-edged sword. Perfusion may enable daytime transplantation, replacing the midnight urgency of cold storage with scheduled, physiologically informed decision-making, and it creates new opportunities for assessment and translational research. At the same time, it changes traditional training experiences and introduces new technical and cognitive competencies, from interpreting perfusion parameters to managing complex extracorporeal circuits. The transplant workforce must evolve alongside the technology, with training programs, staffing models, and professional expertise redesigned to match the capabilities of the machines.

Viewed together, the contributions sketch a field in the midst of systemic reorganization. Machine perfusion can expand organ utilization by recovering organs that might otherwise be lost and by providing additional information to guide acceptance decisions. It is transforming the organ from something that is simply preserved into something that can be assessed, treated, and potentially repaired. Technologies such as NRP and ex vivo perfusion are becoming increasingly interconnected within more complex donation pathways, requiring coordination across organ procurement organizations, donor hospitals, recovery teams, transplant centers, and perfusion platforms. Successful integration will depend not only on technological capability but on the infrastructure, ethical frameworks, and systems of care required to deliver these technologies safely and equitably. In this sense, machine perfusion is emerging as an enabling platform across the entire transplantation pathway rather than a single preservation technology.

The editorial closes with questions that will define the next decade. Perfusion requires personnel, infrastructure, expertise, and financial resources that are not uniformly available, and the field must determine not simply whether these technologies improve individual graft outcomes but how they affect organ utilization, access to transplantation, cost, sustainability, workforce demands, and equity. Enhanced data collection and multicenter collaboration will be essential to identify which approaches provide meaningful benefit, for which organs and recipients, and under what circumstances. What began as a strategy for keeping organs cold has become, in the authors’ framing, a catalyst through which transplantation itself can be reimagined, provided the field builds the systems, safeguards, and shared standards to match the ambition of its machines.

Subject of Research: Machine perfusion technologies for abdominal organ preservation, assessment, and transplantation

Article Title: Editorial: Advancing machine perfusion: navigating challenges in abdominal organ transplantation

Article References: Brubaker, A. L., & Schnickel, G. T. (2026). Editorial: Advancing machine perfusion: navigating challenges in abdominal organ transplantation. Frontiers in Transplantation, 5, Article 2001083. https://doi.org/10.3389/frtra.2026.2001083

Image Credits: AI Generated

DOI: 10.3389/frtra.2026.2001083

Keywords: machine perfusion, organ transplantation, normothermic perfusion, hypothermic machine perfusion, normothermic regional perfusion, liver transplantation, kidney transplantation, organ preservation, ischemia-reperfusion injury, organ donation, transplant surgery, organ viability

The clinical stakes are far from abstract. Organ shortages have made older donor livers a routine part of transplantation, and outcomes still track donor age in ways that stubbornly resist prediction. A registry-based analysis of more than 111,000 liver transplants cited in the review found that when older grafts went to younger recipients, five-year graft survival fell to 69.9 percent, compared with 77.8 percent for young-to-old combinations. Grafts from donors over 60 to 70 years fared particularly poorly in high-risk recipients with MELD scores of 35 or above, and in living donation, use of donors aged 50 and older carried a 61 percent increased hazard of graft failure. The paradox that frustrates clinicians is that age alone incompletely predicts post-transplant behavior. Some older livers retain substantial reserve while others collapse under metabolic overload, inflammatory injury or impaired recovery, which is precisely why the authors argue for a biologically grounded, module-based framework rather than another hunt for a single decisive marker.

That framework rests on five interrelated biological modules that emerged from converging multi-omics evidence: lipid stress and metabolic remodeling, diminished oxidative reserve, proteostatic strain, inflammatory sensitization, and reduced recovery capacity. Each module is supported by different layers of molecular data, and each connects back to mitochondria, the organelles that power fatty-acid oxidation, oxidative phosphorylation, redox homeostasis and detoxification in hepatocytes. The logic is that impaired mitochondrial metabolic flexibility, weakened redox buffering, disrupted organelle crosstalk and failing quality-control systems provide the common substrate on which all five disturbances build. Critically, the authors stress that these modules remain partly compensated at baseline. Molecular age-related changes accumulate quietly while histology and standard blood tests look normal, and only become conspicuous when the liver is challenged by metabolic overload, ischemia-reperfusion injury, cold preservation or ex vivo machine perfusion.

The lipid stress module illustrates how the pieces interlock. Multi-omics studies across mouse strains, diets and ages show that age-associated hepatic phenotypes are shaped not just by time but by genotype and diet, with alterations in fatty-acid handling, lipid-droplet distribution, peroxisomal programs and FGF21 and FABP4 signaling narrowing metabolic flexibility even when baseline function appears preserved. One mechanistic study linked senescence-associated 13-hydroxyoctadecadienoic acid, an oxidized lipid mediator, to age-related steatosis by showing that it directly inhibits catalase, a key antioxidant enzyme. That finding stitches lipid stress to the oxidative reserve module: aged rodent and primate livers repeatedly show altered glutathione balance, elevated reactive oxygen and nitrogen species, increased malondialdehyde, mitochondrial DNA damage and changes in catalase, superoxide dismutase and respiratory-chain proteins. In other words, lipid overload and antioxidant decline are not separate problems but two faces of the same mitochondrial vulnerability.

Proteostatic strain adds a third thread. Rodent phosphoproteomic data and primate single-nucleus studies converge on altered chaperone, protein-degradation and endoplasmic reticulum stress pathways, suggesting that the energetic cost of maintaining protein quality rises with age even in hepatocytes that look intact. The review links this to lipid and redox stress through a mechanistic chain: excess mitochondrial calcium and reactive oxygen species increase ER protein-folding demand, while ATP limitation weakens chaperone and degradation capacity, so proteostatic strain may act as a downstream amplifier of metabolic overload rather than an isolated defect. Inflammatory sensitization operates at the multicellular level. Single-cell studies identify altered endothelial, macrophage, neutrophil and hepatocyte programs in aged liver, and challenge models show that IL-1α signaling between liver sinusoidal endothelial cells and hepatocytes, along with Cxcl2-positive macrophage recruitment of neutrophils, can amplify ischemia-reperfusion injury in old livers. Finally, recovery capacity, the ability to restore metabolic, synthetic and structural homeostasis after injury, is compromised by dysregulated Hedgehog signaling, reduced hepatocyte plasticity and extracellular matrix remodeling, meaning two grafts can absorb similar early stress yet diverge sharply in lactate clearance, bile production and survival.

Why does mitochondria sit at the center rather than the periphery of this network? The review describes a feedback architecture in which lipid overload increases mitochondrial calcium loading and ROS generation, which promotes ER stress and inflammatory signaling; the resulting proteostatic and inflammatory burden then consumes energy and limits repair, further impairing mitochondrial quality control and metabolic flexibility in a self-reinforcing loop. This structure generates testable predictions. A liver carrying combined lipid stress and low redox reserve should show a larger stress-induced rise in mitochondrial, ER-stress and inflammatory readouts and a slower recovery trajectory than a liver with only one abnormal module. The authors are careful to note that mitochondrial vulnerability is the interface connecting the modules, not a separate module itself and not a validated measure of biological age, but it offers a unifying hypothesis for why aging livers with identical birthdays and similar biopsies can behave so differently under duress.

Not all evidence carries equal weight, and the review is unusually candid about this. Rodent studies provide most of the mechanistic depth, with large mouse multi-omics datasets and naturally aged models showing distributed remodeling across lipid metabolism, immune signaling, stress-kinase networks and protein-state regulation. Non-human primate data, though limited in scale and often drawn from female animals, strengthen confidence that ER stress, degradation pathways and hepatocyte pro-senescence programs are conserved rather than rodent-specific artifacts. Human baseline evidence remains the weakest layer: transcriptomic signals of aging are entangled with steatosis, fibrosis, metabolic disease and medication history, and matched human tri-omics datasets are scarce. Spatial and single-cell studies add a crucial caveat about anatomy, showing that hepatocytes do not age uniformly across the lobule. Pericentral cells preferentially accumulate large lipid droplets while periportal cells show more prominent mitochondrial and epigenetic disturbance, which means small biopsies or bulk assays can miss biologically important local variation.

This is where transplantation and machine perfusion enter as natural experiments. Procurement, cold preservation, reperfusion and metabolic reactivation impose rapid, defined swings in oxygen availability and energetic demand, converting modest baseline differences into clinically meaningful ones. Hypothermic oxygenated perfusion and normothermic machine perfusion have already proven their clinical value in randomized trials, reducing early allograft dysfunction, biliary strictures and organ discard, but their scientific value here lies in the sampling window they create. During HOPE, early perfusate flavin mononucleotide, a marker of mitochondrial injury, was higher in grafts that developed early allograft dysfunction, and in a 50-graft validation cohort the five-minute value yielded an area under the curve of 0.744 for early allograft dysfunction and 0.890 for one-year mortality. During NMP, serial perfusate transaminases, lactate dehydrogenase, von Willebrand factor and platelet changes associated with early dysfunction, while perfusate IL-6, TNF-α and IL-10 correlated with postoperative bilirubin, intensive-care stay or graft loss, and bile pH, bicarbonate and glucose tracked biliary viability.

The authors insist these signals are promising readouts, not decision rules. No published study has validated a combined panel across perfusion protocols, and none of the fluid-based markers is aging-specific; they reflect donor comorbidity, ischemia, procurement and preservation strategy as well as age-related vulnerability. The module framework is explicitly hypothesis-generating rather than outcome-validated, and the review warns against merging FMN trajectories, cytokine measurements and biliary chemistry from different cohorts into a clinical scoring system without prospective, matrix-matched validation. What the framework does offer is translational logic: tissue biopsies capture pathway state, serial perfusate captures stress and recovery kinetics, bile captures cholangiocyte function, and post-transplant outcomes provide the ultimate clinical anchor. Future priorities include paired tissue-fluid biobanks, attention to circadian timing and pre-analytical handling of metabolites, spatially informed biopsy interpretation, and explicit separation of immediate procurement injury from genuine recovery behavior in sampling schedules.

The bigger picture is a conceptual shift in how aging science approaches one of medicine’s hardest assessment problems. Rather than seeking a molecular birth certificate for the liver, the review proposes mapping which vulnerability modules are active in a given organ and how they will respond to defined stress. Candidate intervention targets, including FGF21 and FABP4 in lipid metabolism, the 13-HODE-catalase axis in antioxidant buffering and Hedgehog signaling in regenerative reserve, remain experimental, and the authors caution that any therapeutic claim requires direct evidence of benefit against clinically meaningful endpoints. But the reframing itself is consequential: if the most stable features of liver aging are process-level changes that become functionally visible under stress, then machine perfusion may be not just a preservation technology but a stress-testing platform, a controlled environment in which the hidden mitochondrial biography of an aging liver can finally be read before it matters.

Subject of Research: Mitochondrial vulnerability and multi-omics biological modules of the aging liver and their translational relevance to transplantation

Article Title: Multi-omics perspectives on mitochondrial vulnerability in the aging liver: biological modules and translational implications

Article References: Chen, H., Lu, W., Wang, K., Fang, R., Lee, S., Chen, S., & Liu, Z. (2026). Multi-omics perspectives on mitochondrial vulnerability in the aging liver: biological modules and translational implications. Frontiers in Cell and Developmental Biology, 14, Article 1954948. https://doi.org/10.3389/fcell.2026.1954948

Image Credits: AI Generated

DOI: 10.3389/fcell.2026.1954948

Keywords: liver aging, mitochondria, multi-omics, machine perfusion, liver transplantation, oxidative stress, proteostasis, inflammation, biomarkers, FGF21, ischemia-reperfusion injury, hepatocytes

The most fundamental shift is in who the donors are. For decades, the typical deceased donor was a young person declared dead by neurological criteria, a donation after brain death, or DBD, donor whose heart was still beating and whose organs could be recovered in a relatively controlled operating room environment. That profile has eroded. Driven partly by the decline of the drug overdose epidemic that had supplied a tragic stream of young donors, and partly by the deliberate expansion of eligibility criteria, donation has shifted toward older, medically complex individuals. In parallel, donation after circulatory death, or DCD, has grown dramatically. In DCD, death is declared after the heart stops, which means the organs endure a period of warm ischemia, deprived of oxygenated blood at body temperature, before recovery begins. That physiological insult makes DCD organs riskier to use and far more demanding to preserve, but the review notes that DCD has become an increasingly dominant share of deceased donation in the United States.

This changing donor phenotype collides with a stubborn biological constraint: ischemic time, the interval during which an organ sits without adequate blood flow between recovery and transplantation. Every hour of cold ischemia, the period when an organ is flushed with cold preservation solution and stored on ice, inflicts cumulative injury on delicate tissue such as the cells lining blood vessels and the energy-hungry mitochondria of kidney and liver cells. Traditional static cold storage was adequate for young, robust DBD organs traveling short distances. It is far less forgiving for an older DCD liver or a marginal kidney that must now cross a much larger geographic footprint to reach its recipient. The mismatch between a more fragile organ supply and a more dispersed allocation system is, in the authors’ framing, one of the central engineering problems of modern transplantation.

The technological response has been a rapid migration toward machine perfusion. Instead of passive storage on ice, machine perfusion devices pump preservation fluid through the organ, either chilled, as in hypothermic machine perfusion and hypothermic oxygenated perfusion, known as HOPE, or at body temperature, as in normothermic machine perfusion, NMP. Normothermic systems go further, delivering oxygenated blood or blood substitutes so the organ remains metabolically active, allowing clinicians to assess viability in real time and even to recondition organs that would otherwise be discarded. For lungs, ex vivo lung perfusion has enabled longer travel distances and ischemic times in the composite allocation score era, and clinical trials have shown that lungs can be preserved for up to 24 hours at 10 degrees Celsius without compromising outcomes after transplantation. For livers, normothermic machine perfusion has been shown to transform the logistics of transplantation, extending viable preservation windows and reducing the pressure of the race against the clock.

But this technological rescue comes with a bill. Machine perfusion devices, disposable perfusion circuits, and the trained personnel required to run them are expensive, and their use has grown alongside the shift toward DCD and marginal organs. National analyses of liver transplantation document a steep rise in ex situ machine perfusion use, and studies of cost reveal that these technologies add substantially to the standard acquisition cost of each organ. Compounding the problem, the review highlights troubling center-level variability in who actually receives perfused organs: research has found associations between a transplant center’s use of normothermic machine perfusion and the insurance status of its recipients, raising equity concerns about whether the benefits of expensive technology are distributed fairly. Meanwhile, organ acquisition charges, the costs transplant programs pass on to insurers and Medicare, have been climbing for years, with analyses of organ procurement organization cost reports showing that the price of procuring a kidney or liver has risen well beyond general medical inflation.

Policy changes have poured fuel on this fire. The Organ Procurement and Transplantation Network, operating under federal oversight, has spent the past decade dismantling the old donation service area boundaries that historically gave local patients first claim on local organs. First acuity-based liver allocation and then the composite allocation score, a continuous distribution framework, replaced geographic priority with a points-based system balancing medical urgency, waiting time, and travel-related logistics. The stated goal is laudable: organs should flow to the sickest patients wherever they live, not to whoever happens to be nearest the donor hospital. Kidney allocation moved to a circle-based system, and lung allocation adopted continuous distribution. The consequences for logistics, however, are measurable. Studies have documented a large increase in the volume of organ offers that transplant centers must evaluate, decreased efficiency in kidney placement, and longer travel distances and ischemic times for lungs, all of which multiply the coordination burden on procurement teams and add cost at every step.

Federal pressure has also targeted the performance of the organ procurement organizations themselves, the 50-odd nonprofit entities that hold exclusive contracts to coordinate donation within their territories. The Centers for Medicare and Medicaid Services has tightened its conditions of participation and performance evaluations for OPOs, and the Health Resources and Services Administration launched a modernization initiative for the OPTN aimed at increasing accountability. More recently, the CMS Increasing Organ Transplant Access model, or IOTA, is designed to push transplant hospitals to perform more transplants. Analyses of procurement activity following CMS performance evaluations suggest these interventions are reshaping OPO behavior. The cumulative effect is a system in which every participant, from the OPO to the transplant surgeon, faces intensifying metrics-driven pressure to recover and place more organs, including organs that a more conservative era would have declined.

The result, the review argues, is an industry straining against an architecture designed for a different time. Organ procurement remains vertically integrated: the OPO coordinates the donor, dispatches surgical teams, arranges preservation, and manages transport, while transplant centers absorb the acquisition costs through a reimbursement structure, the standard acquisition cost framework, that has not kept pace with modern practice. The authors point to emerging alternatives, including dedicated procurement entities and on-demand organ recovery services that decouple the surgical recovery step from the local OPO monopoly. Evidence from individual centers suggests that specialized donor surgeon involvement can reduce discards of marginal liver allografts, hinting that professionalized, high-volume procurement teams might extract more usable organs from the same donor pool. Normothermic regional perfusion, an alternative to super-rapid recovery in DCD that restores circulation to abdominal organs before retrieval, illustrates how technique choice at the donor hospital ripples through cost and quality downstream, and it remains a subject of active regulatory debate at HRSA.

What would redesign look like? The authors sketch a future in which procurement, preservation, and transport are disaggregated and each is optimized independently. Dedicated procurement organizations could concentrate surgical expertise and standardize recovery quality. Regional perfusion and preservation hubs, analogous to central laboratories, could receive organs, assess them on machine perfusion platforms, and hold them in extended preservation, using technologies like 10-degree lung storage or overnight normothermic liver perfusion to convert the frantic overnight transplant into a scheduled daytime operation. Modernized reimbursement would need to pay transparently for these services rather than burying them in acquisition charges, and quality metrics would need to align across OPOs, preservation centers, and transplant programs so that no participant is rewarded for shifting cost or risk onto another. The review is careful to note the goal: improved efficiency, cost control, and organ utilization without reducing patient access.

The stakes of getting this right are enormous. More than one hundred thousand Americans remain on transplant waiting lists, and every discarded organ represents a life not saved. Xenotransplantation looms on the horizon as a potential additional supply, but as the review’s own financial analysis of procurement suggests, even pig organs will flow through the same procurement, preservation, and allocation infrastructure, inheriting its inefficiencies unless the system is reformed first. The changing landscape of organ recovery is, at its core, a story about a public trust, the gift of donated organs, being handled by a logistics network that was never designed for older donors, warmer perfusion machines, and continent-wide allocation. Fleischer and Sheetz make the case that the coming decade will decide whether that network is deliberately re-engineered, or whether it simply continues to absorb complexity and cost until something gives.

Subject of Research: Trends in US deceased donor organ procurement, preservation technology, allocation policy, and costs

Article Title: The Changing Landscape of Organ Recovery: Recent Trends and Future Predictions

Article References: Fleischer, C. M., & Sheetz, K. H. (2026). The Changing Landscape of Organ Recovery: Recent Trends and Future Predictions. Current Transplantation Reports, 13(1), Article 32. https://doi.org/10.1007/s40472-026-00530-x

Image Credits: AI Generated

DOI: 10.1007/s40472-026-00530-x

Keywords: organ procurement, deceased donation, donation after circulatory death, machine perfusion, organ allocation, composite allocation score, organ procurement organizations, transplantation policy, ischemic time, organ acquisition costs, normothermic perfusion, health policy

The review, led by Marissa C. Kuo and W. Christian Crannell of Vanderbilt University Medical Center with colleagues across Vanderbilt’s surgical, nephrology, biomedical engineering, and cardiac surgery departments, synthesized preclinical and clinical evidence on 10 degrees Celsius static storage in heart, lung, liver, and kidney transplantation. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis scoping review guidelines, the team searched PubMed, Embase, Web of Science, and Scopus on May 22, 2025, returning 1,182 articles. After duplicate removal and independent screening by two reviewers, 45 studies met inclusion criteria, supplemented by 8 studies retrieved from reference lists and 15 additional references covering perfusion strategies, mitochondrial biomarkers, and controlled rewarming. The result is the most complete picture to date of a preservation approach that is quietly reshaping transplant practice.

The strongest evidence comes from lung transplantation. In animal models, storage at 10 degrees Celsius compared with conventional ice has been associated with improved oxygen uptake, lower airway pressures, greater lung compliance, less edema, better arterial oxygenation, and lower pulmonary vascular resistance after transplantation. Biochemical markers of inflammation, including interleukin-8 and interleukin-1 beta, were lower after reperfusion in organs kept at the warmer temperature. Metabolomic studies add mechanistic depth: in a porcine model, lungs stored at 10 degrees Celsius showed upregulation of protective metabolites such as glutathione and ascorbate, downregulation of substrates that induce mitochondrial depolarization, and elevated mitochondrial respiration supported primarily by complexes I and II. Lipid byproducts dominated the metabolite profile, suggesting that beta-oxidation may serve as an alternative energy substrate that keeps graft metabolism gently active, an organ-protective state the authors liken to hibernation.

Clinical experience in lungs has moved rapidly from proof of concept to multicenter trials. A 2021 pilot study of five bilateral lung transplants using 10 degrees Celsius storage reported zero cases of grade 3 primary graft dysfunction, no need for postoperative extracorporeal membrane oxygenation, and 100 percent 30-day survival. A retrospective matched cohort study found that preservation times extending up to 24 hours at 10 degrees Celsius produced no differences in mechanical ventilation time, intensive care or hospital stay, primary graft dysfunction rates, or survival compared with ice storage. A single-institution prospective study and the largest trial to date, a multicenter non-randomized prospective study of 70 donor lungs stored at 10 degrees Celsius overnight and transplanted the next morning, both found outcomes equivalent to conventional storage, with the multicenter trial reporting primary graft dysfunction rates of 5.7 percent versus 9.3 percent in controls. An international randomized non-inferiority trial has recently completed enrollment and may settle the question definitively.

The clinical implications extend beyond graft function into the logistics of transplantation itself. Because organs stored at 10 degrees Celsius tolerate longer cold ischemic times, surgical teams can schedule transplants during daytime hours rather than performing emergency operations in the middle of the night. Case reports describe hearts transported more than 10 hours without machine perfusion, from Anchorage, Alaska to Nashville, Tennessee, and sequential transplantation of two lungs from a single donor into two different recipients at different institutions. For a field in which more than 23,000 waitlisted patients died awaiting a kidney transplant in the United States between 2020 and 2024, and nearly 31,000 died waiting for any organ, every hour of safe preservation time translates into more organs reaching more patients.

Heart transplantation data, though earlier in its development, are similarly encouraging. A propensity-matched cohort study using a reusable 10 degrees Celsius cooler for organ transport found lower lactate changes and slightly higher cardiac index at 24 and 72 hours postoperatively compared with ice storage, though primary graft dysfunction rates did not differ and donor characteristics were not perfectly balanced. A more recent study of hearts procured after thoracoabdominal normothermic regional perfusion found that 10 degrees Celsius storage was associated with reduced risk of primary graft dysfunction, lower postoperative vasoactive inotropic scores, decreased use of renal replacement therapy, shorter intensive care stays, and reduced six-month mortality. Animal work dating back decades supports the temperature window: canine and rat studies found mitochondrial structural changes were less severe below 14 degrees Celsius, and that high-energy phosphate content was severely depleted only when storage temperatures exceeded 10 degrees Celsius.

The biochemical rationale centers on the mitochondria. At deep hypothermic temperatures near 4 degrees Celsius, the oxygen-binding equilibrium of myoglobin strongly favors the oxygenated form, but cytosolic oxygen diffusion slows dramatically and mitochondrial respiration becomes markedly attenuated. In this near-static state, the mitochondrial proton-motive force collapses, forcing ATP synthase to run in reverse and hydrolyze ATP, while electron flow reverses through succinate dehydrogenase, causing succinate to accumulate, a metabolic hallmark of ischemia. Upon reperfusion, rapid oxidation of that succinate generates a burst of superoxide radicals that can trigger mitochondrial permeability transition pore opening, cytochrome c release, and apoptotic signaling. Released mitochondrial DNA then circulates as a damage-associated molecular pattern, activating innate immune pathways that contribute to graft inflammation and rejection. Moderate cooling to around 10 degrees Celsius, by contrast, appears to preserve slow, reversible electron transport, maintain mitochondrial ultrastructure, and keep myoglobin-mitochondrial oxygen coupling intact.

Evidence in liver and kidney transplantation remains thinner and more mixed. In a comprehensive porcine model of donation after circulatory death, 10 hours of 10 degrees Celsius static storage followed by normothermic perfusion produced superior hemodynamic profiles, more bile with higher pH and bicarbonate, and metabolomic evidence of less citric acid cycle dysfunction and mitochondrial oxidative damage than ice storage, but no human liver studies have yet been published. Older kidney studies yielded conflicting results, with some suggesting slightly higher temperatures may better preserve adenine nucleotide levels, and species differences in mitochondrial temperature responses complicate extrapolation to humans. A 2024 rat cell study found the highest viability at 10 degrees Celsius, and a single human deceased donor kidney transplant after 10 degrees Celsius storage achieved immediate graft function, the first patient in a larger prospective trial now underway.

The review also situates 10 degrees Celsius storage within the broader landscape of preservation technology, including oxygenated hypothermic perfusion and controlled rewarming. Randomized trials of hypothermic oxygenated perfusion in liver transplantation have shown fewer non-anastomotic biliary strictures and less early allograft dysfunction, while a kidney trial of extended criteria donors showed no benefit, possibly because organs were stored on ice before perfusion began. Controlled oxygenated rewarming studies suggest that a gentler temperature gradient at reperfusion protects mitochondrial coupling, a benefit that 10 degrees Celsius storage could amplify by starting closer to physiological temperature. Notably, no study has directly compared static 10 degrees Celsius storage with machine perfusion, and the authors suggest that a simple, inexpensive cooler could in some cases obviate the need for costly perfusion devices.

The authors are careful about the limits of the evidence. Definitive conclusions, they write, await well-designed randomized clinical trials capable of providing the highest quality evidence, and the data are far stronger for heart and lung storage than for liver and kidney. Yet the convergence of mechanistic plausibility, decades of animal data, and increasingly positive clinical experience has given the field reason to reconsider a fundamental assumption: that colder is always better. If ongoing randomized trials confirm the early signals, the humble bag of ice that has defined organ preservation since the advent of transplantation may give way to a precisely controlled 10 degrees Celsius, a change that costs little, requires no complex machinery, and could extend the reach of every donated organ.

Subject of Research: Static organ storage at 10 degrees Celsius as an alternative to conventional ice preservation in deceased donor heart, lung, liver, and kidney transplantation

Article Title: 10° Celsius Static Storage in Deceased Donor Organ Transplantation: A Narrative Review

Article References: Kuo, M. C., Breeding, E., Kiyimba, F., Gohar, E. Y., Walden, R. L., Bacchetta, M., & Crannell, W. C. (2026). 10° Celsius Static Storage in Deceased Donor Organ Transplantation: A Narrative Review. Current Transplantation Reports, 13(1), Article 31. https://doi.org/10.1007/s40472-026-00528-5

Image Credits: AI Generated

DOI: 10.1007/s40472-026-00528-5

Keywords: organ transplantation, organ preservation, 10 degrees Celsius storage, static cold storage, mitochondria, ischemia-reperfusion injury, lung transplantation, heart transplantation, cold ischemia time, machine perfusion, deceased donor, primary graft dysfunction