Frontiers in transplantation最新文献

{"title":"Advancing cardiac xenotransplantation: overcoming challenges and ethical considerations for clinical integration.","authors":"Ahmed A Abdelrehim, Daniel J Hurst, W Hampton Gray, Robert Sorabella, Luz A Padilla","doi":"10.3389/frtra.2026.1971770","DOIUrl":"https://doi.org/10.3389/frtra.2026.1971770","url":null,"abstract":"<p><p>Advanced heart failure affects over 6 million adults in the United States alone. Orthotopic heart transplantation remains the definitive treatment, with over 90% one-year survival and meaningful gains in functional status and quality of life. The therapy is, however, constrained by an intractable supply problem. For decades, xenotransplantation (XTx), the transplantation of organs across species, has been proposed as a means of closing this gap, though for most of that time it remained a theoretical aspiration. With the discovery of CRISPR-Cas9 gene editing, improved immunosuppressive strategies, and refined preclinical models, the field has accelerated at an unprecedented pace. Multi-gene-edited porcine donors have survived for more than 200 days in orthotopic non-human primate models, and two compassionate-use pig-to-human cardiac transplants at the University of Maryland (2022 and 2023) demonstrated some feasibility for clinical cardiac XTx for the first time. In May 2026, the FDA granted clearance under an investigational new drug application to allow the EXPRESS study, the first prospective clinical trial of a gene-edited porcine heart, to proceed. In this perspective, we discuss the ethical, regulatory, and equity considerations that remain as decisive barriers to clinical integration and may shape how this therapy is introduced along the remaining immunologic and virologic challenges. We outline what we regard as the near-term priorities: defining the antibody targets that drive xenograft rejection, standardizing virologic surveillance, candidate selection and outcome benchmarking, and building access patterns with embedded distributive justice from the outset of its implementation.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1971770"},"PeriodicalIF":0.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: How current and future approaches and research results contribute to evolve the field of vascularized composite allotransplantation.","authors":"Martin Kumnig","doi":"10.3389/frtra.2026.1993324","DOIUrl":"https://doi.org/10.3389/frtra.2026.1993324","url":null,"abstract":"","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1993324"},"PeriodicalIF":0.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond pulmonary arterial hypertension: sotatercept across the advanced heart failure and transplant continuum.","authors":"Andrew Xanthopoulos, Christos Kourek, Dimitrios E Magouliotis, Filippos Triposkiadis, Alexandros Briasoulis","doi":"10.3389/frtra.2026.1966659","DOIUrl":"https://doi.org/10.3389/frtra.2026.1966659","url":null,"abstract":"","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1966659"},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neu5Gc and beyond: sialylation at the innate immune and thromboinflammatory interface of xenotransplantation.","authors":"Jae Young Kim","doi":"10.3389/frtra.2026.1968710","DOIUrl":"10.3389/frtra.2026.1968710","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Recent advances in genetic engineering have substantially reduced the major carbohydrate barriers to pig-to-human xenotransplantation. Deletion of GGTA1, CMAH, and B4GALNT2 decreases &lt;i&gt;α&lt;/i&gt;Gal, Neu5Gc, and B4GALNT2-dependent Sda-like xenoantigens and thereby attenuates preformed antibody binding and complement-mediated injury. However, removal of these major xenoantigens does not necessarily generate a human-compatible cell-surface glycome. In particular, CMAH knockout eliminates Neu5Gc but leaves a Neu5Ac-dominant sialome whose linkage, chemical modification, glycoconjugate carrier, density, and spatial presentation are not necessarily human-like. This review examines sialylation and glycan-dependent recognition as an underappreciated regulatory layer linking innate immunity, blood-cell homeostasis, complement regulation, and thromboinflammation in xenotransplantation. Two conceptual distinctions are emphasized. First, the direction and evidence depth of glycan-receptor recognition must be explicitly considered. The best-established Siglec-1-dependent xenogeneic interaction is a graft-versus-host pathway, in which donor porcine Siglec-1-positive macrophages capture recipient human erythrocytes. Conversely, direct receptor-level binding of human Siglec-1 to CMAH-deficient gene-edited pig erythrocytes has recently been demonstrated, providing evidence for the reciprocal host-versus-graft direction; however, whether this interaction drives recipient macrophage phagocytosis or &lt;i&gt;in vivo&lt;/i&gt; clearance remains unresolved. Donor ASGR1-dependent uptake of human platelets provides another direct example of glycan-dependent recipient blood-cell clearance. Second, &lt;i&gt;α&lt;/i&gt;2,3-linked Neu5Ac illustrates a fundamental functional trade-off in sialome engineering. Neu5Ac&lt;i&gt;α&lt;/i&gt;2,3Gal-containing glycans can serve as preferred ligands for Siglec-1-mediated capture, whereas &lt;i&gt;α&lt;/i&gt;2,3-linked sialoglycans also contribute to Factor H-dependent recognition of self-associated surfaces and alternative complement regulation. Conversely, increasing &lt;i&gt;α&lt;/i&gt;2,6-linked sialylation may reduce macrophage xenoreactivity and enhance inhibitory Siglec engagement but decrease &lt;i&gt;α&lt;/i&gt;2,3-dependent Factor H recognition; thus, ST6GAL1 engineering should not be considered uniformly protective or equivalent to glycan \"humanization\". Other pathways, including CD24-Siglec-10 signaling, Siglec-9-mediated regulation of neutrophil activation and NETosis, and platelet Siglec signaling, provide additional mechanistic frameworks but remain incompletely validated in solid-organ xenotransplantation. We therefore propose that post-editing glycan compatibility should be evaluated according to receptor directionality, evidence depth, and functional trade-offs, rather than glycan abundance or donor genotype alone. Organ-, cell-, carrier-, and receptor-specific analyses integrating quantitative glycomics/glycoproteomics, human receptor and immune-cell assays, functional crossmatching, a","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1968710"},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychosocial assessment and follow-up in vascularized composite allotransplantation candidates: clinical observations from the Finnish experience.","authors":"Benita Antas, Jan Nyberg","doi":"10.3389/frtra.2026.1845139","DOIUrl":"https://doi.org/10.3389/frtra.2026.1845139","url":null,"abstract":"<p><p>Psychosocial assessment is increasingly recognized as a central component in the evaluation of candidates for vascularized composite allotransplantation (VCA), yet published clinical perspectives remain limited. Drawing on longitudinal clinical observations of five candidates assessed for VCA, three of whom subsequently underwent transplantation in the Finnish VCA program at Helsinki University Hospital, this article reflects on key considerations shaping psychosocial assessment and follow-up. Psychosocial assessment in VCA requires longitudinal, multidisciplinary information gathering, with the clinical picture evolving across successive encounters. Three interrelated domains appear particularly relevant to clinical assessment: psychosocial functioning, cognitive capacity, and social context. We further propose that the concept of mentalization may offer a useful lens for understanding individuals' abilities to reflect on their illness, expectations, interpersonal relationships, and possible changes following transplantation.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1845139"},"PeriodicalIF":0.0,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in <i>ex vivo</i> machine perfusion for abdominal organ transplantation.","authors":"Danae G Olaso, Victoria A Bendersky, Wyeth D Alexander, Aleah L Brubaker, Peter A Than, Gabriel T Schnickel","doi":"10.3389/frtra.2026.1919998","DOIUrl":"10.3389/frtra.2026.1919998","url":null,"abstract":"<p><p>Organ transplantation remains the definitive treatment for end-stage organ failure, yet its impact continues to be constrained by a persistent shortage of suitable donor organs. Despite advances in surgical technique, immunosuppression, and recipient management, organ preservation has remained relatively unchanged for decades. Machine perfusion (MP) has emerged as a transformative advancement in organ preservation, shifting the paradigm from passive storage to active organ support. By actively circulating perfusate under controlled conditions, MP enables metabolic support, mitigation of ischemic injury, and functional assessment prior to implantation. These modalities collectively represent a paradigm shift from passive preservation toward active resuscitation and repair. This review synthesizes current advances in MP across abdominal organ transplantation, emphasizing the scientific rationale, technical evolution, organ-specific applications, and translational challenges. By examining key clinical trials, emerging biomarkers, and future directions we aim to delineate the roadmap for integrating MP into routine clinical practice and realize its full potential in expanding the donor pool and improving graft outcomes.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1919998"},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential missed opportunities for organ donation: incidence and risk factors for non-referral among critically ill patients.","authors":"Leda Nobile, Chiara Faso, Gaia Furlan, Filippo Annoni, Vincent Labbé, Mehdi Mezidi, Valerio Lucidi, Thierry Gustot, Jean-Louis Vincent, Fabio Silvio Taccone","doi":"10.3389/frtra.2026.1924053","DOIUrl":"10.3389/frtra.2026.1924053","url":null,"abstract":"<p><strong>Introduction: </strong>Many potential organ donors are not referred to the transplant coordination, constituting potential missed referrals.</p><p><strong>Methods: </strong>In this retrospective analysis, we explored risk factors for potential missed referral among patients suffering from acute brain injury, who were admitted to a 32-bed mixed intensive care unit (ICU) between 2018 and 2023 and died after hypoxic-ischemic encephalopathy, traumatic brain injury, or subarachnoid hemorrhage (SAH). Patients with absolute contraindications for donation were excluded. Each patient was categorized as \"actual donor\", \"medical refusal\", \"personal refusal\", or \"potential missed referral\". The primary outcome was the potential missed referral rate.</p><p><strong>Results: </strong>Of 183 potential donors, 101 (55%) were referred and 82 (45%) were not; on ICU admission, patients in the potential missed referral group were older, had higher severity scores, more comorbidities, and were less likely to have a diagnosis of SAH. In a binomial logistic regression analysis, older age and chronic obstructive pulmonary disease were independent predictors of potential missed referral; donation after brain death and SAH were associated with higher referral rates.</p><p><strong>Conclusions: </strong>This audit identifies areas for improvement to expand the donor pool, including greater recognition of the donor potential of critically ill patients with extra-neurological complications, even in the presence of older age and comorbidities.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1924053"},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflections on liver transplantation: emerging research and clinical perspectives in 2025.","authors":"Alfred Wei-Chieh Kow","doi":"10.3389/frtra.2026.1923144","DOIUrl":"10.3389/frtra.2026.1923144","url":null,"abstract":"<p><p>The 30th Annual Congress of the International Liver Transplantation Society (ILTS), held in Singapore from 28 to 31 May 2025 under the theme \"Advancing Liver Transplantation: Embracing Innovation for the Future,\" was a landmark meeting-the first ILTS Congress in Southeast Asia and the largest in the Society's history, convening more than 1,200 delegates and 262 invited speakers from 40 countries across 92 scientific sessions and 7 pre-congress workshops. The congress was led by the National University Centre for Organ Transplantation (NUCOT) at the National University Hospital (NUH), with the author serving as Local Chair. This article provides a reflection on the emerging research and clinical perspectives as presented and discussed at the ILTS Annual Congress 2025 in Singapore. We also share the overall organization and experience of the meeting. This is a structured overview of the congress includes its programme architecture, main scientific findings across all subspecialty domains and the legacy Tree of Life project. There is also an in-depth thematic review of the most impactful scientific contributions, with particular attention to robotic and minimally invasive surgery, machine perfusion and donation after circulatory death (DCD) liver transplantation, transplant oncology, artificial intelligence (AI) and precision medicine, and basic and translational science. Collectively, these themes reflect a field at a genuine inflection point, where multiple technological revolutions are converging at clinical maturity whilst enduring challenges of organ scarcity, global equity, and cost sustainability demand continued attention.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1923144"},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal normothermic regional perfusion in controlled DCD: toward a multidisciplinary model of organ resuscitation.","authors":"Raphaël Giraud, Benjamin Assouline, Yvan Gasche, Franz Immer, Karim Bendjelid, Philippe Compagnon","doi":"10.3389/frtra.2026.1930941","DOIUrl":"10.3389/frtra.2026.1930941","url":null,"abstract":"","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1930941"},"PeriodicalIF":0.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged <i>ex vivo</i> lung perfusion with corrected perfusate: functional and structural benefits in swine.","authors":"Justin Issard, Julia Mercier, Jean-Baptiste Ménager, Guillaume Fadel, Yuya Nobori, Melwan Izem, Maria-Rosa Ghigna, Elie Fadel, Fabrice Antigny, Pierre Mordant, Olaf Mercier","doi":"10.3389/frtra.2026.1899960","DOIUrl":"10.3389/frtra.2026.1899960","url":null,"abstract":"<p><strong>Background: </strong>During <i>ex vivo</i> lung perfusion (EVLP), perfusate pH, electrolyte, and glucose concentrations often deviate from physiological ranges. We evaluated the effect of a corrective solution on maintaining these parameters within physiological limits during 12 h of EVLP in a porcine model.</p><p><strong>Methods: </strong>Twelve porcine lung blocks were harvested and cold-preserved before undergoing 12 h of normothermic EVLP. Lung blocks were randomly assigned to two groups based on the perfusate replacement strategy. All lungs were perfused with Steen solution, mean priming volume was 1,525 ± 340 and 1,325 ± 232 mL, with 100 mL (5%-9%) replaced every two hours by either fresh Steen solution (standard group, <i>n</i> = 6) or a modified solution designed to restore physiological composition (corrected group, <i>n</i> = 6). Perfusate electrolytes, glucose, cytokines, pH, partial oxygen pressure (PO₂), pulmonary vascular resistance (PVR), and compliance were measured. After EVLP, left lungs were transplanted during 4 h into donor-related pigs, while right lungs were analyzed by histology and electron microscopy.</p><p><strong>Results: </strong>Perfusate correction successfully maintained electrolyte, pH, and glucose levels within target ranges during EVLP. The corrected group demonstrated higher lung compliance and oxygenation, reduced edema, more hyaline membranes, and a greater density of Kohn's pores after EVLP. PVR was similar between groups, and no significant difference in <i>Δ</i>PO₂ was observed post-transplantation.</p><p><strong>Conclusion: </strong>Maintaining physiological perfusate composition improved lung function during 12-hour EVLP in swine; however, no post-transplant benefit was observed. Further studies are warranted to assess the impact of this strategy during prolonged EVLP and to compare it with alternative approaches.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1899960"},"PeriodicalIF":0.0,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13533982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}