Xenotransplantation最新文献

{"title":"Characteristics Associated With Acceptance of Porcine Xenotransplantation.","authors":"Jennifer L Wainright, Brendon M Cummiskey, Kelsi A Lindblad, Morgan Stuart, Samantha M Noreen, Laura A Cartwright","doi":"10.1111/xen.70084","DOIUrl":"10.1111/xen.70084","url":null,"abstract":"<p><strong>Background: </strong>Understanding public attitudes toward porcine xenotransplantation is critical as it develops toward clinical implementation, which could address the national organ shortage. This study measured public support and identified demographic and personal characteristics associated with acceptance.</p><p><strong>Methods: </strong>We conducted an online survey between April 8 and July 8, 2024. An adult, representative sample (n = 1021) of the US population was obtained through Prolific Survey Services, with oversamples for religious and racial minority groups (total n = 1466).</p><p><strong>Results: </strong>Overall support was high, with 58.1% supporting its use and another 28.3% conditionally supporting it. Support varied by demographic characteristics, with White (88.8%) and Hispanic (88.6%) respondents more supportive than Black (72.2%) and Asian (80.4%) respondents. Men (87.7%) were slightly more supportive than women (84.8%). Muslim respondents (54.6%) were notably less supportive than other religious groups. Multivariable logistic regression confirmed Black respondents were less supportive than White (OR = 0.41, 95% CI: 0.24-0.71, p = 0.001), and Muslim respondents were less supportive than Protestant (OR = 0.18, 95% CI: 0.08-0.37, p < 0.001). Respondents with liberal political orientation (OR = 3.18, 95% CI: 1.92-5.31, p < 0.001) and those knowing a transplant recipient (OR = 2.05, 95% CI: 1.32-3.26, p = 0.002) were more supportive. Primary concerns included zoonotic disease transmission (63.1%) and patient safety (61.4%).</p><p><strong>Conclusions: </strong>While support for porcine xenotransplantation is high overall, notable differences exist across demographic groups. These findings illustrate the importance of targeted educational approaches to address concerns as clinical trials begin, particularly for groups historically disadvantaged in access to transplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70084"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515173","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":"Language Will Matter in Pediatric Cardiac Xenotransplantation Implementation: Terminology for Transplantation Should Align With Childhood Stages and Clinical Scenarios.","authors":"Anthony Merlocco, Luz A Padilla, Daniel J Hurst","doi":"10.1111/xen.70118","DOIUrl":"https://doi.org/10.1111/xen.70118","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70118"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487585","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":"CMAH-Targeted Knock-In of Inducible Heme Oxygenase-1 and Constitutive CD47 in GGTA1-Knockout Pigs for Xenotransplantation.","authors":"Haesun Lee, Sang Eun Kim, Won Kil Lee, Miae Oh, Seunghoon Lee, Jin-Gu No, Mi-Ryung Park, Seokho Kim, Min Hwa Do, Keon Bong Oh","doi":"10.1111/xen.70124","DOIUrl":"10.1111/xen.70124","url":null,"abstract":"<p><strong>Background: </strong>Pig xenografts offer a solution to human organ shortage; however, immune rejection is a major barrier. Immunomodulatory genes such as heme oxygenase-1 (HO1) and CD47 are key. Precise promoter control and strategic genomic integration for reliable expression and xenoantigen disruption are critical. Therefore, this study aimed to develop a promoter-pairing strategy for HO1 and CD47 in genetically modified pigs to achieve context-appropriate expression and enhance xenograft success.</p><p><strong>Methods: </strong>We analyzed the transcriptional profiles of xenoantigens (GGTA1, B4GALNT2, and CMAH) in pig tissues using qPCR. Exon 4 of CMAH was selected for knock-in because of its low activity and xenoantigen role, enabling precise promoter-driven transgene expression and xenoantigen disruption. A dual-promoter cassette (inducible HO1 and constitutive CD47) was inserted into the CMAH locus of GGTA1-knockout fibroblasts using CRISPR/Cas9. The screened clones were used for somatic cell nuclear transfer to generate pigs.</p><p><strong>Results: </strong>CMAH showed significantly lower and more consistent expression than did GGTA1/B4GALNT2 across tissues. In 293T cells and primary pig fibroblasts, HO1 was low at baseline but strongly induced by human serum/PMA, whereas CD47 exhibited high basal expression with inducibility. Cloned pigs with the HO1/CD47 cassette in the CMAH locus were successfully generated and validated. HO1 protein localized mainly to the liver and lungs, while CD47 was broadly expressed in tissues/blood leukocytes, confirming the tissue-specific and stimulus-responsive functions of the dual promoter.</p><p><strong>Conclusion: </strong>This study successfully established a promoter-optimized locus-specific knock-in strategy for inducing HO1 and constitutive CD47 in GGTA1-knockout pigs. This dual-promoter system enabled context-appropriate expression and enhanced xenograft compatibility. Future in vivo studies are crucial to evaluate long-term graft survival and HO1 inducibility, paving the way for clinical xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70124"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575766","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":"The Emergence of the Asian Xenotransplantation Association: Regional Collaboration in a Rapidly Evolving Field.","authors":"Hidetaka Hara, Ik Jin Yun, Yi Wang","doi":"10.1111/xen.70125","DOIUrl":"10.1111/xen.70125","url":null,"abstract":"<p><p>Global progress in xenotransplantation has accelerated following recent first-in-human applications of gene-edited porcine organs. While pioneering clinical experiences have largely been reported from the United States, scientific, translational, and early clinical activities are also expanding across Asia, particularly in China. In this context, regional coordination and sustained dialogue are increasingly important. The establishment of the Asian Xenotransplantation Association (AXA) represents a collaborative initiative to strengthen scientific exchange and foster cooperation among investigators in China, Korea, Japan, India, and the broader Asian community. The first AXA Congress, held in Haikou, China, in December 2025, marked the formal launch of this effort. With the second AXA Congress scheduled for August 24-25, 2026 in Chengdu, China, AXA aims to continue promoting communication, harmonization of research approaches, and the development of the next generation of investigators. Through inclusive and responsible collaboration, AXA seeks to contribute constructively to the global advancement of xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70125"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628697","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":"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":3.8,"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":"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":3.8,"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":"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":3.8,"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":3.8,"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}