Toward a New Era: Major Advancements and Future Perspectives in Organ Medicine

Traditional medical research has primarily focused on the macroscopic systemic, microscopic cellular, or molecular-scale levels. However, because of the historical lack of mature ex vivo organ culture technologies and experimental models, research at the organ level has lagged substantially over the past few decades. This gap has created a formidable cross-dimensional barrier, hindering the clinical translation of basic research findings [1]. In the 2024–2025 period, synergistic breakthroughs in core technologies, specifically ex vivo machine perfusion, immune modification, and xenotransplantation, have catalyzed explosive growth in organ-centric medical research. Although bottlenecks—such as donor shortages, immune rejection, and the limits of ex vivo organ preservation—have yet to be fully overcome, organ medicine has demonstrated immense potential in simulating complex human physiological and pathological environments and in implementing regional precision interventions. Against this backdrop, leading international teams have achieved multiple milestone successes by developing advanced ex vivo organ maintenance technologies, establishing cross-species immune tolerance models, and implementing organ-quarantined therapies in situ. This editorial aims to systematically review the 10 core achievements in organ medicine this year, providing a critical reference for promoting the standardization of organ medicine and the advancement of clinical precision diagnostics and therapeutics. A collaborative effort by Beicheng Sun's team at the First Affiliated Hospital of Anhui Medical University and Hongjiang Wei's team at Yunnan Agricultural University (China) [2] achieved a historic breakthrough in the field of xenotransplantation by successfully performing the world's first auxiliary liver transplant from a 10-gene-edited pig to a living human patient. The research team selected Diannan miniature pigs as donors. Using CRISPR/Cas9 technology, they knocked out three xenoantigen-encoding genes (GGTA1, CMAH, and β4GalNT2) and overexpressed seven human genes involved in complement regulation, coagulation regulation, and macrophage inhibition to mitigate the risks of hyperacute and acute rejection. The gene-edited porcine liver was implanted into the right hepatic fossa of a patient following the resection of a massive tumor, providing functional support via an orthotopic auxiliary approach. Postoperatively, the patient exhibited no signs of hyperacute or acute rejection, infection, or severe complications within the first 31 days. Both the xenograft and the patient's remnant autologous liver maintained stable metabolic function. Although the xenograft was surgically removed on postoperative day 38 due to the onset of xenograft thrombotic microangiopathy, subsequent therapeutic management successfully controlled complications, and the patient survived until postoperative day 171. This study provides clinical evidence confirming the functional viability and metabolic compatibility of multigene-edited porcine livers in the human body. Furthermore, it identified xenograft thrombotic microangiopathy as the primary pathological barrier limiting the long-term survival of hepatic xenografts, thereby accumulating invaluable data for the future clinical application of xenogeneic organ transplantation. Dawn Bowles' team [3] at Duke University Medical Center (USA) used an ex vivo normothermic perfusion system to successfully construct a novel platform for ex vivo organ gene transduction, effectively addressing the challenge of “off-target” effects inherent in systemic gene therapy. In their study, these investigators introduced adeno-associated virus vectors carrying a luciferase reporter gene directly into the perfusion circuit of donor hearts during a 2-h normothermic perfusion window immediately following explantation. Subsequent transplantation revealed that transgene expression in the graft was both rapid (detectable within 48 h) and durable (persisting for 120 days). Crucially, gene expression was highly specific and localized strictly to the graft myocardium, with no detectable off-target effects in the recipient's liver, lungs, or psoas muscle, nor did it induce tissue structural damage or functional impairment. This research confirms that leveraging the normothermic ex vivo perfusion platform for gene modification can effectively circumvent the systemic toxicity associated with intravenous delivery. It offers a safe, highly efficient, and clinically translatable pathway for using genetic engineering to resolve transplant rejection or ischemia–reperfusion injury. Alessandra Bertacco's team [4] at the Padova University Hospital (Italy) constructed an integrated extracorporeal life support platform, setting a new world record by maintaining a human liver under physiological conditions (37°C) for 17 days (424 h) ex vivo. The team innovatively coupled an NMP system with a continuous renal replacement therapy device. Using a human liver that had been discarded due to colorectal cancer metastasis, the researchers employed continuous renal replacement therapy to simulate renal function, providing real-time clearance of metabolic waste products to support prolonged maintenance. Throughout the 17-day perfusion, the liver maintained stable hemodynamics and exhibited continuous, active physiological functions, including albumin synthesis, lactate clearance, and bile secretion, while preserving the histological integrity of the hepatic tissue. This study demonstrates that the introduction of an “artificial kidney” is the key determinant in achieving ultra-long-term organ maintenance ex vivo. Furthermore, by utilizing this mechanical perfusion platform, the team established an ex vivo human tumor model, providing an unprecedented long-term platform for tumor biology research, pharmacological testing, and future organ repair strategies. Xiaoshun He's team at the First Affiliated Hospital of Sun Yat-sen University (China) successfully restored functional activity in porcine brains ex vivo following 50 min of cardiac arrest, proposing a disruptive “heart–lung–liver–brain” resuscitation strategy. The research team used their proprietary “ex vivo brain maintenance” device to construct a circulatory system incorporating an artificial heart, an artificial lung, and an ex vivo functioning liver. When porcine brains were connected to this system and perfused for 50 min ex vivo, cerebral edema was significantly attenuated. Crucially, neuronal viability and microstructural integrity were markedly improved, and sustainable electroencephalographic activity was restored, an outcome unattainable with traditional cardiopulmonary resuscitation alone. This study challenges traditional paradigms regarding the limits of cerebral ischemic tolerance and, for the first time, establishes the core status of the liver–brain axis in reversing the pathophysiology of brain death. It provides a novel, holistic resuscitation paradigm for the clinical salvage of patients with cardiac arrest. Sandra Lindstedt's team [5] at Lund University (Sweden) provided the first proof-of-concept in a large animal model that xenogeneic mitochondrial transplantation is both safe and effective in mitigating lung ischemia–reperfusion injury. The team established an ex vivo porcine lung perfusion model and administered a single dose of fresh mitochondria isolated from murine livers via the pulmonary artery into the injured porcine lungs. The xenogeneic mitochondrial therapy significantly improved the oxygenation function of the transplanted lungs without inducing acute immune rejection or tissue damage. Mechanistically, the treatment prompted a significant elevation in tissue levels of the anti-inflammatory cytokine IL-10 while inhibiting the proinflammatory cytokine IL-6, demonstrating potent anti-inflammatory and reparative effects. This research confirms the biosafety of using murine tissue as an “off-the-shelf” mitochondrial donor source and validates the cross-species biocompatibility of mitochondria. It offers a highly promising new strategy for repairing marginal donor organs and preventing primary graft dysfunction in clinical transplantation. Ton Rabelink's team [6] at Leiden University Medical Center (Netherlands) developed a subnormothermic mechanical perfusion platform utilizing a cell-free perfusate, successfully achieving the metabolic and functional preservation of human kidneys for up to 4 days ex vivo. The researchers engineered a 25°C subnormothermic machine perfusion system using a nutrient-supplemented perfusate devoid of red blood cells, enriched with tricarboxylic acid cycle intermediates. The system integrated urine recirculation and continuous hemofiltration to maintain electrolyte balance and clear metabolic waste. This strategy successfully sustained active aerobic metabolism and key physiological functions in the kidneys for 4 days. Spatial metabolomics confirmed that the kidneys maintained stable energy flux throughout the perfusion period. This study indicates that functional organ preservation for several days is achievable without the need for oxygen-carrying red blood cells. It provides a critical, extended time window for the repair, regeneration, and complex immunomodulatory treatment of marginal donor kidneys ex vivo. Christian Wolfrum's team [7] at ETH Zurich (Switzerland) elucidated a novel mechanism regulating hepatic lipid metabolism and successfully applied it to achieve defatting and repair of human livers ex vivo. The team first characterized the “Golgi PtdIns4P–CUL7FBXW8–ATGL” signaling pathway. Using an NMP system, they subsequently treated severe steatotic human livers ex vivo with a specific small-molecule inhibitor, UCB9608, over an 8-day intervention period. This intervention significantly reduced the degree of steatosis in preclinical human donor liver models without observable toxicity. This study establishes a hormone-independent, autonomous cellular lipid regulation axis. It demonstrates that targeting the PI4KB/PtdIns4P pathway is not only a potential therapeutic target for metabolic dysfunction-associated steatohepatitis but also a breakthrough strategy for converting discarded marginal donor livers into high-quality, transplantable organs. Xiaoshun He's team [8] at the First Affiliated Hospital of Sun Yat-sen University (China) developed the Life-XDL, the world's first machine perfusion system designed specifically for whole, diseased human livers, establishing an “ex vivo human diseased whole-organ model.” The team collected six discarded diseased livers from patients undergoing total hepatectomy for end-stage liver disease. These organs were connected to the Life-XDL system for NMP, simulating the human physiological environment. The system successfully maintained the survival of these diseased livers ex vivo for up to 60 h. During this time, the livers retained stable hemodynamic characteristics, exhibited significant recovery of metabolic function, and preserved the microstructural integrity of both the hepatic parenchyma and tumor tissues. This research overcomes the technical challenges of maintaining diseased organs ex vivo, bridging the gap left by cellular and animal models that cannot fully replicate the complex pathology of human liver disease. It provides an experimental platform with immense clinical translational value for elucidating disease mechanisms, screening new drugs, and assessing toxicity. A global consortium led by Philipp Dutkowski [9] at the University Hospital Zurich (Switzerland), involving 10 transplant centers across seven countries, conducted a large-scale multicenter study validating the predictive value of FMN for assessing donor liver quality. The study analyzed perfusate data from 473 human livers during hypothermic oxygenated perfusion, focusing on monitoring the fluorescence intensity of FMN released from mitochondrial complex I and correlating it with post-transplant outcomes. The results confirmed that perfusate FMN levels are highly correlated with graft loss, nonanastomotic biliary strictures, and renal failure. The study defined specific FMN safety thresholds to stratify donor livers by risk, demonstrating a predictive efficacy significantly superior to conventional scores. This study represents the first international validation of FMN's predictive value, providing an objective, rapid, and precise risk stratification tool for the safe utilization of marginal donor livers, particularly those from donation after circulatory death. Xiaoshun He's team [10] at the First Affiliated Hospital of Sun Yat-sen University (China) pioneered OQT, realizing organ-level precision treatment and protection independent of the systemic circulation. This technology employs surgical or interventional techniques to temporarily block the vascular communication between the target organ and the systemic circulation. Through cannulation, the organ is connected to an extracorporeal NMP system to construct an independent circulatory loop. In this isolated state, high-concentration pharmacological perfusion or ischemic protection can be administered. The team successfully performed the world's first organ-quarantined protection procedure on a transplanted kidney, protecting it from prolonged warm ischemia during surgery. They also expanded this strategy to in situ chemotherapy for liver tumors, achieving high-concentration perfusion of chemotherapeutic agents within the isolated organ while maintaining zero drug exposure in the systemic circulation. This research establishes a novel “physical isolation, targeted perfusion” treatment paradigm. It not only solves the challenge of organ ischemic protection during complex surgeries but also minimizes systemic drug toxicity, making OQT a safe, efficient, and low-toxicity therapeutic option. The 10 breakthrough advances of the 2024–2025 period profoundly outline the grand vision of “organ medicine” as a new discipline at the organ level of life sciences. This marks a pivotal shift in the center of gravity for medical research and treatment—advancing rapidly from traditional microscopic cellular mechanism exploration and macroscopic individual intervention toward precision repair and functional remodeling centered on the “organ” as the core unit. By deeply integrating molecular-level technologies, such as gene editing, microscopic cellular-level mitochondrial transplantation, and organ engineering approaches like NMP and OQT, these technological breakthroughs are fundamentally reshaping our understanding of disease pathogenesis and clinical treatment strategies. The vigorous rise of organ medicine not only offers a disruptive pathway to resolving the global organ shortage crisis through xenotransplantation and the repair of marginally damaged organs but also signifies that humanity has initially mastered the core capabilities to “reprogram” diseased organs ex vivo, and to implement “organ-quarantined” precision therapy in situ. Looking ahead, the field of organ medicine faces both opportunities and challenges. We anticipate that deepened interdisciplinary collaboration will be essential to overcome existing barriers and advance the translation of basic research into clinical practice. As a key academic platform in this field, Organ Medicine remains committed to disseminating high-quality research and fostering innovative thinking, contributing to the comprehensive revolution of organ medicine. Yuanwei Shi: investigation, writing – original draft. Qiang Zhao: conceptualization, supervision, writing – review and editing. Xiaoshun He: conceptualization, supervision, writing – review and editing. During the preparation of this work, the authors used Google Gemini to translate and improve the readability of the manuscript. The prompts used included requests to “translate into professional medical English” and “polish the language.” After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. The authors have nothing to report. The authors have nothing to report. The authors have nothing to report. Professor Xiaoshun He is the Editor-in-Chief of the Organ Medicine Editorial Board. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. The remaining authors declare no conflicts of interest. Data sharing is not applicable to this article as no datasets were generated or analyzed.