Xenotransplantation最新文献

{"title":"Xenotransplantation Literature Update: July-December 2025.","authors":"Kasra Shirini, Joseph M Ladowski, Niket Harsh, Raphael P H Meier","doi":"10.1111/xen.70123","DOIUrl":"10.1111/xen.70123","url":null,"abstract":"<p><p>The second half of 2025 marked a significant transition for xenotransplantation, shifting further from experimental feasibility to early clinical translation. Prolonged physiologic support from genetically engineered porcine kidneys and livers in human recipients provided unprecedented insight into organ compatibility, rejection dynamics, and species-specific physiology. Parallel advances in molecular profiling refined the understanding of innate and humoral immune injury, while innovations in donor-pig engineering, immunomodulation, and biosafety frameworks strengthened translational readiness. Preclinical non-human primate studies continued to inform clinical trial design, particularly regarding proteinuria, complement incompatibility, and novel xenoantigens. Alongside these scientific advances, growing attention to ethics, patient selection, and public trust highlighted the societal dimensions of clinical implementation. Collectively, these developments underscore the rapid maturation of xenotransplantation and define the scientific and regulatory foundations for ongoing first-in-human trials.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70123"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575734","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":"Realistic Prospects of Xenotransplantation in Japan: Specific Regulations for Clinical Application.","authors":"Kazuki Morita, Yuichiro Ukon, Satoshi Hosoya, Eisuke Minegishi, Hideyuki Hakui, Jun Sugihara, Manabu Hasegawa","doi":"10.1111/xen.70112","DOIUrl":"https://doi.org/10.1111/xen.70112","url":null,"abstract":"<p><p>Xenotransplantation has emerged as a potential solution to the critical shortage of donor organs, with recent breakthroughs demonstrating transplantation of genetically modified porcine organs into humans. In Japan, the Ministry of Health, Labour and Welfare has advanced the regulatory review framework to accelerate research and enable the nation's first clinical xenotransplantation. Unlike conventional pharmaceutical pathways, the Act on the Safety of Regenerative Medicine provides a distinctive framework that allows xenotransplantation to be delivered as a medical procedure rather than as a medicinal product. Under this law, a multi-step review process and adherence to specific guidelines, this framework may facilitate early-phase clinical research while safeguarding public health, offering an alternative model to regulatory systems in the other countries.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70112"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378720","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":"Xenotransplantation and Human Organ Trafficking: The Impact of Increased Organ Availability.","authors":"Daniel J Hurst, Luz A Padilla, Emanuele Cozzi, Jay Fishman","doi":"10.1111/xen.70121","DOIUrl":"10.1111/xen.70121","url":null,"abstract":"<p><p>The global shortage of organs for allotransplantation contributes to illicit trade in human organs. While clinical xenotransplantation is proposed as a potential solution to this global shortage, diverse factors contribute to human organ trafficking including global shortages, underdeveloped and under supported organ procurement infrastructures and related legislation, inadequate access to advanced medical therapies or insurance coverage, and poverty and corruption allowing exploitation of vulnerable populations. This article assesses competing predictions regarding the relationship between the advent of xenotransplantation and the global black market for organs. Some argue that a plentiful supply of xenografts will reduce or eliminate the demand that drives organ trafficking. This analysis highlights significant countervailing risks regarding (i) cost, availability, and equitable access; (ii) perceived quality / desirability of an allograft versus a xenograft; and (iii) the emergence of new illicit markets. We conclude that the effect of xenotransplantation on organ trafficking is presently unpredictable but an important metric for success in this field.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70121"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499889","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":"\"Will I Still be Myself?\" Opposition to Xenotransplantation Among Chinese Kidney Transplant Candidates: A Qualitative Study.","authors":"Wenhao Tang, Jiaxing Zhou, Shangping Zhao, XiaoQing Li, XiaoQing Chen, Yingli Yang, Chunmei Wang, Bo Gu, Qiling Tan","doi":"10.1111/xen.70127","DOIUrl":"https://doi.org/10.1111/xen.70127","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation remains the preferred treatment for end-stage renal disease (ESRD), yet its application is constrained by a persistent shortage of donor organs. Xenotransplantation has emerged as a promising alternative, but its clinical adoption faces complex ethical, cultural, and psychological barriers.</p><p><strong>Methods: </strong>Using a phenomenological approach, we conducted semi-structured face-to-face interviews with 18 kidney transplant candidates who opposed xenotransplantation at West China Hospital of Sichuan University between June and August 2025. Data were analyzed inductively using NVivo software in conjunction with Colaizzi's seven-step method.</p><p><strong>Results: </strong>Four interrelated themes captured the key barriers to acceptance: (1) Anxiety about physical self-identity and social pressure-fears of losing bodily integrity or facing stigma; (2) Concerns about medical safety-perceived risks of rejection, infection, and technological uncertainty; (3) Information barriers and decision-making dilemmas-fragmented information and lack of professional guidance; and (4) Lack of trust and security mechanisms-mistrust in both the technology and institutional safeguards.</p><p><strong>Conclusions: </strong>The acceptance of xenotransplantation among Chinese kidney transplant candidates who oppose xenotransplantation is hindered by multidimensional, interlinked factors involving identity, safety, knowledge, and trust. Addressing these specific barriers through targeted transparent education, ethical governance, and institutional trust-building strategies is essential for the responsible clinical integration of xenotransplantation and also provides a reference for communicating with skeptical candidates in clinical practice.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70127"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646868","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":"Vatican Reaffirms Moral Permissibility of Xenotransplantation.","authors":"Daniel J Hurst, Umberto Agrimi, David K C Cooper, Emanuele Cozzi, Jay A Fishman, Cesare Galli, Sigrid Müller, Maria Concetta Pellicciari, Carlo Maria Petrini, Richard N Pierson, Mario Picozzi, Frans J van Ittersum, Renzo Pegoraro","doi":"10.1111/xen.70122","DOIUrl":"https://doi.org/10.1111/xen.70122","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70122"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499925","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":"Expression of Human Thrombomodulin Prevents Early Thrombocytopenia and Thrombotic Microangiopathy in Pig-to-Nonhuman Primate Orthotopic Liver Xenotransplantation.","authors":"Zhongqiang Zhang, Ting Li, Qiang Li, Bin Xie, Xinger Zhao, Jianbin Wang, Yaxun Huang, Jing Luo, Shali Wen, Yinchun Zhou, Yong Deng, Yanfang Lu, Yanyan Jiang, Jiequn Li, David K C Cooper, Dengke Pan, Zhongzhou Si, Haizhi Qi","doi":"10.1111/xen.70120","DOIUrl":"10.1111/xen.70120","url":null,"abstract":"<p><strong>Background: </strong>Severe thrombocytopenia and coagulation dysregulation remain major barriers to survival in pig-to-primate liver xenotransplantation models.</p><p><strong>Methods: </strong>Porcine livers with five genetic modifications (GTKO, CMAHKO, β4GalNT2KO, hCD55, and hTBM) were orthotopically transplanted into four Tibetan macaques under two conventional immunosuppressive protocols. Longitudinal monitoring included graft and multi-organ function, hematology, coagulation, and immune responses. Histopathological and immunohistochemical analyses were performed to characterize graft and recipient pathology.</p><p><strong>Results: </strong>High expression of human thrombomodulin (hTBM) in donor livers effectively prevented early rapid and severe thrombocytopenia, with three of four recipients maintaining platelets >100 × 10⁹/L. Thrombotic microangiopathy (TMA) was absent in grafts and recipient organs despite transient hypercoagulability. No spontaneous bleeding occurred in three of four cases. However, porcine livers failed to synthesize functional coagulation factor II, protein C, and protein S, contributing to progressive coagulopathy. While early graft function and coagulation remained stable for four posttransplant days, late dysfunction ensued, characterized by impaired coagulation factor synthesis and progressive graft failure. Antibody-mediated rejection, accompanied by IgM/IgG/C4b deposition, anti-TKO antibody increase, and pvWF upregulation, triggered injury that was amplified by innate and T cell-mediated responses.</p><p><strong>Conclusions: </strong>GTKO/CMAHKO/β4GalNT2KO/hCD55/hTBM donor liver transplantation was associated with an absence of early severe thrombocytopenia, transfusion requirement, and TMA, but long-term survival was limited by immune-mediated rejection and cross-species incompatibilities in coagulation factor synthesis. Optimizing (i) donor genetic modifications and (ii) immunosuppressive therapy, with (iii) replacement of targeted coagulation factors will be crucial for achieving durable survival in pig liver xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70120"},"PeriodicalIF":4.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499864","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":"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":"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":"https://doi.org/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":4.1,"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":"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":4.1,"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":"https://doi.org/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":4.1,"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}