Xenotransplantation最新文献

{"title":"Donor-Derived Cell-Free DNA (dd-cfDNA) as an Early Noninvasive Biomarker of Graft Injury in Pig-to-Monkey Islet Xenotransplantation.","authors":"Ji-Jing Yan, Jong-Min Kim, Sang-Ik Cho, Hyori Kim, Kyungmin Kwak, Hyunil Kim, Eun-Jee Oh, Jaeseok Yang, Chung-Gyu Park, Jong Cheol Jeong, Beom Seok Kim","doi":"10.1111/xen.70126","DOIUrl":"10.1111/xen.70126","url":null,"abstract":"<p><strong>Background: </strong>In pig-to-nonhuman primate islet transplantation, reliable, sensitive biomarkers are needed to detect graft damage at an early stage before irreversible islet loss occurs. In our study, we investigated donor-derived cell-free DNA (dd-cfDNA) as an early, noninvasive biomarker of graft injury by analyzing its correlation with porcine C-peptide levels, complement activation markers, and donor-specific antibodies (DSAs).</p><p><strong>Methods: </strong>Streptozotocin-induced diabetic cynomolgus monkeys received 50 000-100 000 IEQ/kg of intraportal islets from quadruple-knockout (QKO; GGTA1, CMAH, B4GALNT2, and A3GALT2) pigs. Cohort 1 received antithymocyte globulin (ATG), tacrolimus, mycophenolate mofetil (MMF), and anti-inflammatory agents (i.e., anakinra, adalimumab, and tocilizumab), whereas Cohort 2 received the same regimen plus rituximab and crovalimab. Graft function and immune responses were assessed by measuring porcine C-peptide levels, complement activation markers, histology, and dd-cfDNA kinetics.</p><p><strong>Results: </strong>Cohort 1 showed transient porcine C-peptide secretion with marked dd-cfDNA elevation at 7 d postoperatively that coincided with complement activation (i.e., C5a and membrane attack complex (MAC)) and dense CD3⁺ T-cell and CD68⁺ macrophage infiltration, which resulted in early graft loss. Cohort 2 maintained stable C-peptide levels, lower dd-cfDNA levels, and reduced complement activation with improved graft preservation. Moreover, dd-cfDNA correlated negatively with C-peptide and positively with C5a but not with MAC. In both cohorts, DSA levels remained unchanged.</p><p><strong>Conclusions: </strong>Our study revealed that dd-cfDNA levels correlate with graft damage and C5a in QKO porcine islet xenografts, which corroborates dd-cfDNA utility as an early biomarker for predicting instant blood-mediated inflammatory reaction (IBMIR). These findings indicate that dd-cfDNA may be able to detect early islet xenograft damage.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70126"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Research Trends and Current Status of Xenotransplantation: A Bibliometric Analysis.","authors":"Shujun Yang, Xilong Lin, Hao Wei, Jiang Peng, Panfeng Shang, Shengkun Sun","doi":"10.1111/xen.70104","DOIUrl":"10.1111/xen.70104","url":null,"abstract":"<p><p>Xenotransplantation has garnered significant attention in recent years, characterized by substantial progress and rapid developments within the field. The objective of this study was to investigate the evolving trends and emerging research hotspots in xenotransplantation through a comprehensive bibliometric analysis. We conducted an analysis of literature published between 1980 and 2025, sourced from the Web of Science Core Collection. Data processing, analysis, and visualization were performed using VOSviewer, CiteSpace, the Bibliometric R package, and Scimage Graphica. A total of 7880 articles spanning 45 years were included in the analysis. The United States emerged as the predominant contributor to the field, both in terms of article output and institutional involvement. Professor David K. C. Cooper was identified as the leading author, with the highest number of publications on xenotransplantation. The journal Xenotransplantation was found to be the most prolific in terms of article publication. Key research hotspots identified through this analysis include the selection of gene-editing strategies for pigs, the use of genetically modified pigs as donors for various cells, tissues, and organs, as well as the focus on clinical trials and translational studies aimed at advancing xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70104"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human CD64 Alleviates Antibody-Mediated Rejection in Xenotransplantation.","authors":"Chuheng Gou, Hong Zhang, Rui Ding, Quancheng Wang, Li Zhang, Xin Hong, Liqiang Zhao, Kefeng Dou, Xuan Zhang","doi":"10.1111/xen.70110","DOIUrl":"https://doi.org/10.1111/xen.70110","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation, using gene-edited pigs, represents an important approach to overcoming human organ shortages. A major obstacle to xenotransplantation is antibody-mediated rejection (AMR), which leads to xenograft injury by activating complement and effector cells through the fragment crystallizable domain (Fc) of donor-specific antibodies (DSAs). Therefore, we designed a strategy to express the human high-affinity IgG receptor (hCD64) on porcine endothelial cells to competitively bind IgG and protect xenografts from AMR.</p><p><strong>Methods: </strong>The lentiviral transduction of hCD64 into porcine aortic endothelial cells (PAEC) from wild-type and GTKO pigs was validated using quantitative reverse transcription (qRT)-PCR, Western blot, and flow cytometry. The effects of hCD64 transduction and activation on cell physiology were assessed using RNA sequencing. The IgG Fc-binding capacity of hCD64 was validated using flow cytometry and ELISA. Finally, the protective effect of hCD64 against complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in PAECs and GTKO PAECs was confirmed through apoptosis assays.</p><p><strong>Results: </strong>hCD64 was stably expressed at both mRNA and protein levels in PAEC^hCD64 and PAEC^GTKO/hCD64, with both exhibiting normal physiological functions. PAEC^hCD64 and PAEC^GTKO/hCD64 bound free human IgG in a concentration-dependent manner. In contrast, hCD64 did not bind to human IgM or pig and mouse IgG. In the CDC assay, the survival of PAEC^hCD64 was significantly higher than that of PAEC^NC (67.89% vs. 46.03%); moreover, the survival in GTKO PAEC had the same trend (85.18% vs. 71.09%). Similar results were obtained in the assay of ADCC: the survival rates of PAEC^hCD64 and PAEC^NC were 67.27% and 44.95%, respectively, and the survival of PAEC^GTKO/hCD64 and PAEC^GTKO/NC were 80.73% and 66.62%, respectively. Pre-saturation with high doses of human-derived mAbs did not abrogate the protective function of hCD64.</p><p><strong>Conclusion: </strong>hCD64 expression may partially protect xenografts from AMR through its ability to bind competitively with DSAs IgG Fc.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70110"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically-Engineered Pigs as a Source of Blood Products.","authors":"Aaron C K Lucander, David K C Cooper","doi":"10.1111/xen.70114","DOIUrl":"https://doi.org/10.1111/xen.70114","url":null,"abstract":"<p><p>Whole blood and its constituents are primary treatments for numerous human patients with a vast array of clinical conditions. Each year, these include >10 million blood transfusions performed in the USA and approximately 16 million patients globally that receive plasma-derived medicinal products costing $30 billion. As the clinical indications and demand for blood products continue to grow, there is a critical impetus for establishing sources that are more reliable, cost-effective, and efficacious than the current system that is largely built around samples derived from human donors. In particular, genetically-engineered pigs that have been developed for solid organ xenotransplantation could also serve as a source of blood products, representing a potential source for fulfilling global clinical needs. Here we provide an overview of the blood product economy and assess the feasibility of genetically-engineered pigs as a source of clinical-grade blood products for use in human recipients. Although the potential need for these products is immense, we draw attention to the special requirement for them in patients with pig organ grafts.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70114"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic Validation of PERV-C-Free Pigs to Support Xenotransplantation.","authors":"Neal R Benjamin, Giovanni Madrigal, Yasuko Ishida, Julian Catchen, Kari L Allen, Brent Pepin, Alfred L Roca","doi":"10.1111/xen.70109","DOIUrl":"10.1111/xen.70109","url":null,"abstract":"<p><p>Porcine endogenous retroviruses (PERVs) are present in the germ lines of domesticated pigs (Sus scrofa) and related suids. There are three types of PERVs, PERV-A, -B, and -C, which differ in their host range. PERV-A and -B can infect human and porcine cells, while PERV-C only infects porcine cells. PERV-A and -B are found in the genomes of all pigs, while PERV-C is found in most but not all pigs. Although many PERV provirus insertions are defective, in vitro culture of porcine cells has produced infectious virions of all three types as well as PERV-A/C recombinants, which show enhanced replication competence. Identifying pigs that are PERV-C negative could help prevent such recombination events and would advance the development of porcine germplasm as a safer source of xenografts for humans. Here, we present the results of extensive screening involving 142 Landrace, Duroc, Large White, and crossbred pigs using up to nine primer pairs to identify putative PERV-C-negative animals. Long-read whole genome sequencing was conducted on a subset of four pigs (one PERV-C PCR positive and three PERV-C PCR putative negatives), which confirmed their status as PERV-C positive or negative, respectively. Our results confirmed that the screened pigs were truly PERV-C negative, establishing the existence of PERV-C-negative germplasm within the herd. These findings support the feasibility of developing or selecting PERV-C-negative pigs as a source of germplasm for xenotransplantation and other biomedical applications.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70109"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12810672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Xenogeneic Liver Support in a Living Human: Promise, Lessons, and Next Steps.","authors":"Raphael P H Meier","doi":"10.1111/xen.70107","DOIUrl":"10.1111/xen.70107","url":null,"abstract":"<p><p>Genetically engineered porcine organs are redefining the boundaries of clinical xenotransplantation. Zhang et al. now report the first functional pig-to-human liver xenotransplantation in a living patient, demonstrating that a 10-gene-edited auxiliary porcine liver can engraft, produce bile, and synthesize metabolic and coagulation factors in vivo. The xenograft supported a high-risk hepatectomy with borderline remnant volume and contributed to early postoperative stability, although xenotransplant-associated thrombotic microangiopathy ultimately required graft removal. The case highlights both the promise of xenogeneic hepatic support and the physiologic limits that currently preclude durable therapy, including thrombocytopenia, complement-coagulation incompatibility, portal-flow competition, and challenges in assessing dual-graft function. These results establish proof-of-concept for temporary porcine liver support in humans and outline key priorities for next-generation designs: optimized thromboregulation, mitigation of xTMA, improved immunomodulation, and strategies for controlled transition to native-liver autonomy.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70107"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigational New Drug Enabling Nonclinical Study of Xenogeneic Life-Supporting Porcine Kidneys With 10 Gene Edits (10 GE) in a Nonhuman Primate Test System.","authors":"Daniel L Eisenson, Alexander C Schulick, WeiLi Chen, Michelle R Santillan, Michael Cole, Yu Hisadome, Kasra Shirini, Du Gu, Vina Nguyen, Yusuf Ciftci, Alice Zhao, Armaan Akbar, Saghar Babadi, Amanda Maxwell, Kristina DeSmet, Marc Lorber, Leigh Peterson, Lars Burdorf, Kasinath Kuravi, Farzana Rahman, Lori Sorrells, Maria Kokkinaki, Daniel Warren, Betsy King, Russell Wesson, Hamid Rabb, June Jones, Kathleen Funk, Matthew Sturos, Muraly Puttabyatappa, Brijesh Verma, Robin Avery, Thomas Johnson, William Clarke, Robert Brodsky, Maria Bettinotti, Avi Rosenberg, Hayato Iwase, David Ayares, Andrew Cameron, Kazuhiko Yamada","doi":"10.1111/xen.70113","DOIUrl":"10.1111/xen.70113","url":null,"abstract":"<p><p>This Investigational New Drug (IND) enabling study evaluated life-supporting kidney xenotransplantation using porcine source animals with 10 gene edits (10 GE) in a nonhuman primate (NHP) test system. Twelve baboons received xenografts with either calcineurin inhibitor (CNI)-based or CD40/154 costimulation blockade immunosuppression. Source-specific screening prevented early xenograft antibody-mediated rejection in recipients, and clinically relevant preservation with hypothermic machine perfusion-maintained xenograft viability after off-site procurement at a high health herd facility. No zoonotic infections were detected. Six of 12 recipients achieved survival >3 months without evidence of cell- or antibody-mediated rejection. CNI-based regimens were well-tolerated and achieved the longest survivals to date using this approach, contingent on maintenance of therapeutic drug levels. However, xenograft loss among recipients of each immunosuppression regimen was associated with complement activation and microangiopathy, despite 10 GE Xenokidney expression of hCD46 and hCD55. Complement activation, potentially worsened by infection-related inflammation, may lead to long-term 10 GE Xenokidney failure.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70113"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Report of Four Depletional Induction Strategies in Non-Human Primate Islet Xenotransplantation.","authors":"Meghan Hu, Qimeng Gao, Joseph Ladowski, Imran Anwar, Isabel DeLaura, Allison Miller, Matthew Tunbridge, Mingqing Song, Xunrong Luo, Shu Li, He Xu, Allan D Kirk","doi":"10.1111/xen.70108","DOIUrl":"10.1111/xen.70108","url":null,"abstract":"<p><strong>Background: </strong>Porcine islet xenotransplantation is limited by the availability of clinically applicable immunosuppressive regimens. We tested four depletional induction strategies and maintenance regimens in a non-human primate (NHP) islet xenotransplant model.</p><p><strong>Methods: </strong>Genetically modified or wild-type neonatal porcine islets were transplanted via portal vein infusion in diabetic NHPs. Induction consisted of rhesus anti-thymocyte globulin (rhATG) (Group 1, n = 4), anti-CD4 monoclonal antibody (mAb, Group 2, n = 3), or human anti-thymocyte globulin (huATG) tocilizumab (Groups 3 and 4; n = 3 and n = 4, respectively). Maintenance consisted of B7 (Groups 1-3) or anti-CD154 (Group 4) costimulation blockade, tacrolimus transitioned to sirolimus (sirolimus only in Group 4), and mycophenolate mofetil. Xenografts were monitored for blood glucose and porcine c-peptide.</p><p><strong>Results: </strong>Median graft survivals were <14 days (Group 1), <14 days (Group 2), 99 days (Group 3), and 119 days (Group 4). Insulin independence was achieved in one animal in Group 4. Graft survival significantly correlated with islet dose >40,000 IEQ/kg. Rejection was predominately CD3⁺ T-cell mediated. Selective depletion of CD4⁺ T cells led to increased proliferation of CD8⁺ T cells and CD8⁺ infiltrates.</p><p><strong>Conclusions: </strong>Induction with huATG/tocilizumab and maintenance with 5c8 led to the best functional outcomes. CD4 T-cell depletion with anti-CD4 mAb induced compensatory CD8 T-cell proliferation and graft infiltration.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70108"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13037833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Gene Duplication of B4GALNT2 in Pigs for Xenotransplantation- Technical & Practical.","authors":"Caroline G Lucas, Kristin M Whitworth, Melissa M Samuel, Bethany K Redel, Randall S Prather, Kevin D Wells","doi":"10.1111/xen.70115","DOIUrl":"https://doi.org/10.1111/xen.70115","url":null,"abstract":"<p><p>The B4GALNT2 gene has become an important target for xenotransplantation because its inactivation reduces the antigenicity of porcine tissues. The growing use of organ-source pig models has led to an increased demand for the rapid creation of these animals. However, the physiological role of this gene in pigs remains poorly understood. In 2015, after generating pigs lacking B4GALNT2 expression, researchers observed a third allele for this gene. Subsequently, another gene, described as B4GALNT2-like, was found in the porcine genome. We have collected data over four years since the production of our first line of xenotransplantation pigs lacking B4GALNT2 and B4GALNT2-like expression. In this study, we were able to show that pig cells expressing B4GALNT2-like also reacted to Dolichos biflorus agglutinin (DBA) lectin, which recognizes GalNAc epitopes. Additionally, we demonstrated that B4GALNT2/B4GALNT2-like knockout embryos were able to be carried to term in females with the same genotype. We hypothesized that the presence of both genes in the porcine genome might have occurred due to duplication, inversion, and reinsertion of part of the Phospho1-B4GALNT2 segment. Finally, the pig B4GALNT2-like gene showed greater similarity to the human, bovine, and murine B4GALNT2 genes than the original pig B4GALNT2. These data clarify the importance of targeting both B4GALNT2 and B4GALNT2-like for xenotransplantation studies and have improved our knowledge about their genomic structure and role in pig reproduction.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 1","pages":"e70115"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xenograft-Derived Cell-Free Deoxyribonucleic Acid as an Early Biomarker of Rejection in Genetically Engineered Pig-to-Non-Human Primate Kidney Xenotransplantation.","authors":"Kyu-Hyun Han, Joon Young Jang, Minsun Jung, Sun Ae Hwang, Il Hee Yun, Hwan Lee, Minhee Seong, Bomin Kim, Jong Cheol Jeong, Jeong Ho Hwang, Sangil Min, Hyunil Kim, Beom Seok Kim, Ik Jin Yun, Jaeseok Yang","doi":"10.1111/xen.70100","DOIUrl":"https://doi.org/10.1111/xen.70100","url":null,"abstract":"<p><strong>Introduction: </strong>Non-invasive biomarkers that detect xenograft injury before irreversible damage are essential for improving kidney xenotransplantation outcomes. This study investigated whether xenograft-derived cell-free DNA (xdcfDNA) is helpful as a non-invasive, early biomarker of antibody-mediated rejection.</p><p><strong>Methods: </strong>Kidneys from genetically engineered pigs (GGTA1/CMAH/iGb3s/B4GalNT2 knockout; CD39, CD55, CD46, TBM knock-in) were transplanted into 10 cynomolgus monkeys, which received thymoglobulin, rituximab, anti-CD154 monoclonal antibody, corticosteroid, tacrolimus, and mycophenolate mofetil. Plasma xdcfDNA was measured using species-specific quantitative polymerase chain reaction. Pathological scoring and rejection diagnosis of the kidney xenograft biopsy were performed based on the Banff 2022 criteria.</p><p><strong>Results: </strong>XdcfDNA levels increased markedly before an overt increase in serum levels of creatinine and blood urea nitrogen after kidney xenotransplantation. When recipients were classified into low- and high-score groups based on the Banff score of kidney xenograft biopsy, xdcfDNA levels were higher in the high-score groups for intimal arteritis (v), composite vasculitis (g + ptc + v), tubular atrophy (ct), interstitial fibrosis (ci), and IgG deposition. Furthermore, the rejection group showed higher xdcfDNA levels than the non-rejection group (p = 0.0270). The cut-off xdcfDNA value for xenograft rejection was 2.545%, with an apparent sensitivity of 100% (95% confidence interval, 64.57%-100.00%) and specificity of 100% (43.85%-100.00%).</p><p><strong>Conclusions: </strong>XdcfDNA is a potentially sensitive, noninvasive, and early biomarker of xenograft rejection, capturing vasculitis and subsequent chronic injury. Periodic monitoring of xdcfDNA could support noninvasive screening of rejection before overt functional changes in xenografts emerge and might contribute to guiding confirmatory xenograft biopsy and subsequent immunosuppression modification.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 6","pages":"e70100"},"PeriodicalIF":4.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}