Frontiers in transplantation最新文献

{"title":"Xenotransplantation: lessons from history, genetic engineering, and early clinical experience-an interview with Dr. David K. C. Cooper.","authors":"Reza Abdi","doi":"10.3389/frtra.2026.1827646","DOIUrl":"10.3389/frtra.2026.1827646","url":null,"abstract":"<p><p>Xenotransplantation has evolved from speculative experimentation into a scientifically grounded and increasingly applied clinical discipline, propelled by advances in immunology, molecular genetics, and genome engineering. In this interview, Dr. David Cooper, a pioneer in the field, reflects on the historical origins of xenotransplantation and traces key mechanistic breakthroughs, including the identification of carbohydrate xenoantigens, complement incompatibility, and innate immune barriers. Major milestones involving the organ-source pig include the development of αGal-knockout pigs, the expression of human complement-regulatory proteins, and the emergence of highly multi-gene-edited pigs enabled by CRISPR-based technology. Attention is given to kidney-specific challenges, including metabolic and physiologic incompatibilities, coagulation dysregulation, and the continued need for significant immunosuppressive therapy based on blockade of the CD40/CD154 co-stimulation pathway. Differing donor-engineering strategies adopted by various companies, unresolved barriers, such as swine leukocyte antigen (SLA) incompatibility, and lessons from early clinical experience are explored. Together, these insights highlight both the remarkable progress and the substantial challenges that remain before xenotransplantation can become a durable and scalable clinical solution.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1827646"},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13194448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148020241","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":"Case Report: Lung transplant recipient with bullous pemphigoid and antibody-mediated rejection: an overlapping immunologic phenomenon?","authors":"Sandrine Hanna, Daniel Gutteridge, Christiane Machado, Mrunal G Patel, David W Roe, Nichole A Smith, Biplab Saha","doi":"10.3389/frtra.2026.1773797","DOIUrl":"10.3389/frtra.2026.1773797","url":null,"abstract":"<p><p>We present what is, to our knowledge, the first reported case of concurrent bullous pemphigoid (BP) and antibody-mediated rejection (AMR) in a lung transplant patient. Similar associations have been described in other solid organ transplant settings, most notably in renal transplantation, where explantation of the allograft has frequently been followed by resolution of the skin disease. These observations suggest a broader potential connection between autoimmune blistering disorders and allograft rejection mechanisms, especially as emerging evidence highlights the role of non-HLA antibodies. A comprehensive review of previously reported cases of BP in solid organ transplant recipients is therefore warranted to place this case in context and to assess its significance within the existing literature.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1773797"},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825826","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":"Case Report: A rare case of primary graft failure after autologous stem cell transplant for mantle cell lymphoma rescued with darbepoetin, eltrombopag, and cyclosporine.","authors":"Seav Huong Ly, Jordan Chung Cheng Hwang, Yeow Kheong Woon, Chandramouli Nargarajan, Jeffrey Kim Siang Quek, Yeh Ching Linn, Tertius T Tuy","doi":"10.3389/frtra.2026.1811694","DOIUrl":"10.3389/frtra.2026.1811694","url":null,"abstract":"<p><p>We present a case of successful rescue of primary graft failure following autologous hematopoietic stem cell transplantation (autoHSCT) in mantle cell lymphoma using a combination of darbepoetin, eltrombopag, and cyclosporine. Primary graft failure is a rare but serious complication of HSCT that may lead to life-threatening infections, bleeding, and increased overall morbidity and mortality. The underlying mechanisms of graft failure in autoHSCT are not well elucidated, and management options are often limited to autologous stem cell boost or allogeneic stem cell transplantation. Our case highlights the use of a combination of darbepoetin, eltrombopag, and cyclosporine as a potential novel multipronged strategy for rescuing primary graft failure following autoHSCT.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1811694"},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13124695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825843","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":"Building pragmatic transplant immunobiology in Sri Lanka: a concise review with an LMIC lens.","authors":"Anura Priyantha Hewageegana","doi":"10.3389/frtra.2026.1772174","DOIUrl":"10.3389/frtra.2026.1772174","url":null,"abstract":"<p><p>Sri Lanka's kidney transplantation programme has matured within a resource-constrained public health system and has achieved short-term outcomes that appear comparable to published ranges from similar middle-income programmes, despite major limitations in real-time transplant immunobiology support. However, increasing recipient sensitisation, prolonged dialysis vintage, and a growing deceased-donor programme demand more reliable immunological risk assessment to improve equity and graft outcomes. This pragmatic narrative review summarises the minimum immunobiology package that can support safer kidney transplantation in low- and middle-income settings, using Sri Lanka as an example. Key concepts are explained in simple operational terms, including sensitisation and antibody screening (PRA, including the Zora assay), single-antigen bead testing and donor-specific antibody interpretation, practical use and limitations of virtual crossmatch when donor HLA data are incomplete, and the continuing role of CDC crossmatch where flow-cytometry crossmatch is unavailable. The review also highlights why unexpected early rejection may still occur even when HLA-based testing appears reassuring, and why over-reliance on any single assay can be misleading. Finally, a staged roadmap is proposed-prioritising feasible upgrades, quality assurance, workforce development, and national coordination-to progressively strengthen transplant immunobiology while preserving affordability, fairness, and sustainability. This is a pragmatic narrative review informed by consensus guidance and key peer-reviewed literature, synthesised to prioritise actionable, scalable immunobiology components for low- and middle-income settings.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1772174"},"PeriodicalIF":0.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794689","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":"Best practices along the kidney transplantation clinical journey.","authors":"Sara Machado, Stergios Bobotis, Alexander Loupy, Gillian Divard, Valentin Goutaudier, Andreas Pascher, Philipp Houben, Jacopo Romagnoli, Filippo Paoletti, Daniel Casanova, Sofia Zarraga, Mehmet Ergisi, Bryan Ooi, Zoe-Athena Papalois, Elias Mossialos, Vassilios Papalois","doi":"10.3389/frtra.2026.1779662","DOIUrl":"10.3389/frtra.2026.1779662","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation (KTx) practices vary across healthcare systems, yet the operational components of best practice (BP) along the clinical pathway remain incompletely defined. This study aimed to identify key best practice elements across the kidney transplantation journey in four European countries.</p><p><strong>Methods: </strong>A mixed-methods study was conducted across France, Germany, Italy, and Spain. A structured survey (<i>n</i> = 253 respondents, including patients, living donors, nephrologists, transplant surgeons, transplant coordinators, and hospital administrators) assessed clinical practice and patient experience across four domains: CKD management, kidney donation and transplantation, transplant recipient care, and service governance. Semi-structured focus group interviews were performed in each country to contextualise survey findings. Ethics approval was obtained in accordance with national requirements.</p><p><strong>Results: </strong>Key elements for best practices along the KTx clinical journey were identified: (1) development of protocols to standardise the variable monitoring of CKD, to minimize urban-rural differences in clinical practice due to limited resources and follow-up care; (2) enhanced primary care training and targeted resource allocation to diagnose and monitor early-stage CKD; (3) donor coordination and promotion of living donation, addressing gaps in patient awareness and access to care; (4) development of communication protocols on living donation; (5) implementation of targeted patient and donor educational campaigns on living donation; (6) enhanced post-transplant follow-up care by nephrologists; (7) integration of quality-of-life assessments and psychological donor support post-transplantation; (8) increased availability of transplant coordinators to promote equitable resource allocation and the adoption of innovative practices; (9) streamlined governance structures along clinical journey; and (10) equitable funding models with consistent reimbursement policies across patient groups.</p><p><strong>Conclusions: </strong>This study provides a cross-national, mixed-methods framework for strengthening equity, coordination, and quality in kidney transplantation. Addressing variability in monitoring pathways, referral structures, patient-centred outcomes, and workforce capacity may enhance implementation of international transplantation guidelines and improve patient and donor outcomes.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1779662"},"PeriodicalIF":0.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794576","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":"Uterus transplantation in the United States: analysis of patients and early postoperative outcomes in the national organ procurement and transplantation network.","authors":"Thomas Schaschinger, Leonard Knoedler, Tobias Niederegger, Gabriel Hundeshagen, Olivier Mathieu, Lucile Cabanel, Michel G Cazenave, Samuel Knoedler, Curtis L Cetrulo, Alexandre G Lellouch","doi":"10.3389/frtra.2026.1750905","DOIUrl":"10.3389/frtra.2026.1750905","url":null,"abstract":"<p><strong>Purpose: </strong>Uterus Vascularized Composite Allotransplantation (UTx) offers a solution for individuals with uterine factor infertility to enable pregnancy. This exploratory retrospective study evaluates adverse postoperative outcomes in UTx recipients in the U.S. using data from the Organ Procurement and Transplantation Network (OPTN) to identify potential risk factors.</p><p><strong>Methods: </strong>Data from the OPTN database were analyzed for 55 patients who underwent UTx in the U.S. Due to missing outcome data, 15 cases were excluded, resulting in a final cohort of 40 patients (73%) eligible for outcome analysis. Variables such as the number of acute rejection (AR) episodes, hospitalizations, and complications were assessed to determine associations with patient related risk factors.</p><p><strong>Results: </strong>Among the 40 recipients with a mean age of 31 ± 4.7 years, 24 (60%) received grafts from living donors and 16 (40%) from deceased donors. The 12 AR episodes [median 0.0 (IQR 0.0-0.25)] were significantly associated with increased BMI (<i>p</i> = 0.038). The 20 post-transplant hospitalizations [median 0.0 (IQR: 0.0-1.0)] were less frequent in patients who received grafts from living donors (<i>p</i> = 0.016). 9 patients (23%) experienced at least one postoperative complication, with a trend toward higher incidence in patients with increased BMI (<i>p</i> = 0.066) and significantly higher rates linked to prolonged warm ischemia time (<i>p</i> = 0.031).</p><p><strong>Conclusions: </strong>This study provides insights into adverse postoperative outcomes in UTx recipients, highlighting the impact of higher BMI, donor status, and warm ischemia time on AR, hospitalizations, and complications.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1750905"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794683","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":"Cell cycle pathway alterations predict outcomes post-liver transplantation for hepatocellular carcinoma.","authors":"Ashton A Connor, Mahinur Mattohti, Sudha Kodali, Maen Abdelrahim, Ahmed Elaileh, Samar Semaan, Youssef Dib, Khush Patel, Jason Todd, Urmi Sengupta, Constance M Mobley, Caroline J Simon, Yee Lee Cheah, Ashish Saharia, Mary R Schwartz, Sadhna Dhingra, Jessica S Thomas, Randall J Olsen, Linda W Moore, Kirk Heyne, Xian C Li, David W Victor, Timothy E Newhook, Ahmed O Kaseb, Jean-Nicolas Vauthey, A Osama Gaber, R Mark Ghobrial","doi":"10.3389/frtra.2026.1758576","DOIUrl":"10.3389/frtra.2026.1758576","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) incidence and mortality are rising. Liver transplantation (LT) offers the best outcomes, but current tumor size- and number-based selection criteria restrict access. Molecular profiling may better reflect tumor biology and guide precision-based selection strategies.</p><p><strong>Methods: </strong>This prospective single-center study included patients with HCC who had undergone LT between 11 November 2016 and 4 April 2023 with sufficient tumor cellularity in explanted livers. Tumor DNA was subjected to targeted sequencing for 38 genes, with the results returned to clinicians. Altered genes were grouped into HCC-relevant signaling pathways. Outcomes included post-LT overall survival (OS), recurrence-free survival (RFS), and recurrence sites. The Cancer Genome Atlas (TCGA) HCC cohort was used for validation.</p><p><strong>Results: </strong>Among 1,103 LT recipients, 261 were for HCC and 91 underwent sequencing. Most patients were male (<i>n</i> = 68), white (<i>n</i> = 56), and hepatitis C positive (<i>n</i> = 34). The median tumor size was 3 cm (IQR 1.8-4.5), the number was 1 (IQR 1-3), and the follow-up time was 1,982 days. Of the 36 unique mutations found across 11 genes, six were potentially actionable. Cell cycle pathway alterations (<i>n</i> = 14) were prognostic for worse OS (3-year 90.9% without vs. 62.5% with alterations) and RFS in uni- and multivariable models. Recurrences were more common in the liver and lungs with cell cycle alterations (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Post-LT molecular profiling of HCC reveals tumor-specific alterations associated with outcomes, supporting the incorporation of tumor biology into future LT selection criteria.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1758576"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794694","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":"Evaluating the impact of neighborhood socioenvironmental burden on patient characteristics and survival in liver transplant recipients.","authors":"Samar Semaan, Ashton A Connor, Sudha Kodali, Anil K Vadathya, Ahmed Elaileh, Youssef Dib, Khush Patel, Jason Todd, Jennifer Cullen, Caroline J Simon, Yee Lee Cheah, Constance M Mobley, Ashish Saharia, Tamneet Basra, David W Victor, Linda W Moore, A Osama Gaber, R Mark Ghobrial","doi":"10.3389/frtra.2026.1731241","DOIUrl":"10.3389/frtra.2026.1731241","url":null,"abstract":"<p><strong>Background: </strong>The Environmental Justice Index (EJI) measures neighborhood level environmental, social, and health disparities. The Social-Environmental Ranking (SER) components of the EJI is used when linking to health outcomes. Higher SER scores (≥0.75) indicate greater environmental injustice and potential health inequities. This study assesses whether EJI's through SER can inform the care of liver transplantation (LT) patients in Houston, Texas.</p><p><strong>Methods: </strong>This single-center, retrospective analysis was conducted on LT recipients between January 2008 and December 2024. Patient addresses were linked to census tract-level EJI data and stratified at a 0.75 score threshold. Propensity score matching (PSM) was performed. Overall survival (OS) was assessed pre and post matching.</p><p><strong>Results: </strong>A total of 2,030 LT recipients were stratified by SER score (<0.75 vs. ≥0.75). Pre-matching, high SER patients were more often female (44.4% vs. 38.9%, <i>p</i> = 0.02), non-Hispanic Black (14.9% vs. 6.7%) or Hispanic (36.2% vs. 16.1%, <i>p</i> < 0.001), had public insurance (44.0% vs. 33.8%, <i>p</i> < 0.001), were unemployed at transplant (27.4% vs. 31.9%, <i>p</i> = 0.046), and had lower education levels (<i>p</i> < 0.001). They also had higher BMI (28.90 vs. 28.05, <i>p</i> = 0.024), longer waitlist times (103 vs. 71 days, <i>p</i> = 0.036), more diabetes (35.4% vs. 28.4%, <i>p</i> = 0.002), CMV positivity (79.3% vs. 71.0%, <i>p</i> < 0.001), and multi-organ transplants (18.6% vs. 14.4%, <i>p</i> = 0.015). Pre-LT, more were hospitalized on the floor (21.8% vs. 14.0%) and fewer in ICU (40.3% vs. 44.4%, <i>p</i> < 0.001). PSM yielded 619 matched pairs with covariate balance (SMD < 0.1). OS and graft survival did not differ by SER strata before or after matching (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>These findings suggest that EJI is associated with pre-transplant variables and may help identify patients in need of social supports. However, individual patient factors seem to determine post-LT survival.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1731241"},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794730","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":"Exploratory biomarkers for acute rejection in vascularized composite allotransplantation.","authors":"Dominika Pullmann, William J Rifkin, Haruyuki Hirayama, Bruce E Gelb, Ata S Moshiri, Massimo Mangiola, Eduardo D Rodriguez, Catherine P Lu, Piul S Rabbani","doi":"10.3389/frtra.2026.1788046","DOIUrl":"10.3389/frtra.2026.1788046","url":null,"abstract":"<p><p>Vascularized composite allotransplantation (VCA) involves immunologically heterogeneous tissues with a high incidence of acute rejection. Reliable and timely detection of rejection onset remains a major unmet challenge in VCA management. This longitudinal exploratory case study assessed blood- and tissue-derived biomarkers for acute rejection monitoring in a full-face and bilateral hand transplant recipient over 4.6 years. Of these biomarkers, donor-derived cell-free DNA (dd-cfDNA) and short tandem repeats (STR) showed trends toward elevated recipient levels during acute rejection, though differences were not statistically significant. CD8⁺ T-cell percentages increased before acute rejection onset, highlighting a temporal association. Anti-angiotensin II type 1 receptor antibody (AT1R-Ab) levels did not differ significantly between acute rejection and non-rejection episodes, possibly due to prophylactic immune cell depletion. While dd-cfDNA and STR levels correlate with rejection episodes and reflect key graft cellular events, CD8⁺ T-cell dynamics demonstrated the strongest temporal association with rejection episodes in this patient, though no biomarker showed statistically significant differences. These exploratory findings support the need for further longitudinal, multi-patient studies to validate emerging biomarkers and refine rejection monitoring strategies in VCA.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1788046"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147701807","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":"Challenges and perspectives in xenoliver research: lessons from decedent and primate models.","authors":"Zoe Hahn, Kasra Shirini, Joseph M Ladowski, Raphael P H Meier","doi":"10.3389/frtra.2026.1783796","DOIUrl":"10.3389/frtra.2026.1783796","url":null,"abstract":"<p><p>Liver xenotransplantation is a potential strategy to address the shortage of donor livers, either as a temporary bridge to allotransplantation, bridge to native liver recovery, or destination therapy. Advances in genetic engineering and immunosuppression have enabled liver xenografts to evade hyperacute rejection, yet durable graft survival remains elusive. Profound thrombocytopenia, consumptive coagulopathy, and xenotransplantation-associated thrombotic microangiopathy limit long-term graft survival. Evidence from nonhuman primates, decedents, and recent clinical models suggests that hematologic and physiologic species incompatibilities (in addition to classical immune-mediated rejection) constitute additional barriers to successful liver xenotransplantation. These problems are driven by species-specific platelet-endothelial interactions, dysregulated coagulation factor synthesis, and platelet sequestration within the xenograft. This review synthesizes lessons from decedent and primate xenoliver models, highlighting progress in this area to date, barriers to prolonged survival after liver xenotransplant, and directions for further research.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1783796"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577191","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}