Xenotransplantation最新文献

{"title":"Public Awareness and Acceptance of Xenotransplantation: A National Survey in China.","authors":"Hongmin Kuang, Xin Hong, Jingjun Zhao, Jianlin Wang, Kefeng Dou, Xuan Zhang","doi":"10.1111/xen.70117","DOIUrl":"10.1111/xen.70117","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation (XTx), as a crucial direction for addressing the shortage of allogeneic donors, has achieved significant progress and garnered widespread attention in China. However, this field still faces multiple challenges at the ethical, legal, and social levels, making it particularly critical to systematically understand public attitudes and perceptions regarding XTx. This study aims to investigate the knowledge and acceptance of the Chinese population toward XTx.</p><p><strong>Methods: </strong>A 47-item questionnaire was designed to explore the Chinese public's knowledge and acceptance of XTx. It was distributed and collected via the \"Wenjuanxing\" platform (a Chinese online survey tool), getting 2651 valid responses. Nonparametric tests and generalized linear models were performed with SPSS software to test the proposed relationships.</p><p><strong>Results: </strong>The overall public acceptance score for XTx was 98 (82, 104), indicating a moderate level of acceptance (67.59%). Among the dimensions, \"Knowledge and Attitude\" scored the highest (72.72%), while \"Risks and Concerns\" was the lowest (60.00%). Multivariable analyses identified key independent factors influencing acceptance. Males, individuals with higher education, urban residents, and those willing about uncompensated donation had significantly higher total scores. Conversely, females, individuals with religious beliefs, nonmedical professionals, and those with personal/family-related transplant experiences had significantly lower scores. Dimension-specific analyses yielded several insights. Higher income mitigated risk concerns. Additionally, healthcare professionals held more positive views on efficacy and cost than other groups.</p><p><strong>Conclusions: </strong>The Chinese public demonstrates a relatively high level of awareness and a moderately favorable acceptance of XTx. However, respondents exhibit incomplete knowledge of inherent residual risks, immune rejection, and long-term efficacy in XTx. At the same time, they hold overly optimistic expectations regarding its therapeutic outcomes and associated costs.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70117"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499879","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":"Renin-Angiotensin-Aldosterone System (RAAS) in Pig-to-Baboon Kidney Xenotransplantation-Relevance to Clinical Pig Kidney Xenotransplantation.","authors":"Maho Terashita, Kohei Kinoshita, Ryousuke Satou, Akemi Katsurada, Gweneth Eliza Lavalla, Akihiro Maenaka, Yuji Hidaka, Ivy A Rosales, David Ayares, Tatsuo Kawai, Luis Gabriel Navar, David K C Cooper","doi":"10.1111/xen.70129","DOIUrl":"10.1111/xen.70129","url":null,"abstract":"<p><strong>Background: </strong>Pig-to-human kidney xenotransplantation offers a potential solution to the organ shortage. However, the ability of the transplanted pig kidney to regulate blood pressure and fluid balance remains uncertain. The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in these functions, but species differences may impair its effectiveness in xenotransplantation.</p><p><strong>Methods: </strong>Gene-edited pig kidneys were transplanted into six immunosuppressed baboons. Group A (n = 2) underwent bilateral native nephrectomy, while Group B (n = 4) had unilateral nephrectomy with one native kidney remaining in situ (with its ureter ligated) to avoid it contributing to salt and volume regulation. Plasma creatinine, potassium, renin, angiotensinogen, angiotensin I, and aldosterone levels were measured.</p><p><strong>Results: </strong>Group A, but not Group B, exhibited increases in plasma creatinine and potassium levels, indicating hypovolemia that could be corrected by frequent fluid administration. Pig-specific renin was undetectable at all post-transplant time points in both groups. Baboon renin concentration and activity were measurable only in Group B, indicating that the native kidney contributed to renin production. Aldosterone levels remained unchanged in both groups.</p><p><strong>Conclusions: </strong>The absence of detectable pig renin highlights a potential physiological challenge in xenotransplantation. However, the retention of a native kidney may help maintain RAAS function and mitigate fluid and electrolyte imbalances. In clinical pig-to-human kidney transplantation, both native kidneys are usually retained, thus minimizing the development of hypovolemia.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70129"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677174","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":"Liver Xenotransplantation: Ethical and Societal Implications.","authors":"Daniel J Hurst, Christopher A Bobier, Luz A Padilla, Anthony Merlocco, Raphael P H Meier","doi":"10.1111/xen.70116","DOIUrl":"10.1111/xen.70116","url":null,"abstract":"<p><p>The shortage of transplantable livers and high waitlist mortality rates have accelerated the clinical translation of liver xenotransplantation. Recent milestones, including extracorporeal perfusion models and gene-edited pig-to-human transplants in both decedents and living patients, indicate that clinical trials may be imminent. While the ethics of solid organ xenotransplantation generally-such as animal welfare, xenozoonosis, and informed consent-have been debated, the specific implications of liver xenotransplantation remain underexplored. This article examines these unique challenges. We argue that pediatric liver xenotransplantation research might proceed simultaneously with adult research due to high waitlist mortality among infants. In adults, we analyze how liver xenotransplantation intersects with historical controversies regarding patient selection, specifically concerning alcohol-associated liver disease and hepatocellular carcinoma. We explore the ethical risks of a potential dual pathway allocation system that could bifurcate waitlists based on disease etiology, raising concerns regarding distributive justice and the stigmatization of addiction. Finally, we consider whether xenografts might serve as a trial of time for patients currently ineligible for allotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70116"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13002998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487525","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":"Precise Multi-Gene Editing Strategies for Xenotransplantation Donor Pigs: Overcoming Immune and Coagulation Barriers.","authors":"Qianqian Li, Jingchao Cao, Shoulong Deng, Kun Yu","doi":"10.1111/xen.70128","DOIUrl":"10.1111/xen.70128","url":null,"abstract":"<p><p>Organ transplantation is the preferred treatment for end-stage organ failure, but the severe shortage of donors severely restricts its clinical application. Xenotransplantation, especially using pigs as donors, is considered an ideal source of alternative donors due to the high similarity between their organ structures and those of humans. However, significant differences in immune recognition and coagulation regulation between species can easily induce a series of rejection reactions, including hyperacute rejection, acute humoral rejection, T-cell-mediated rejection, and chronic vascular complications. It also carries risks such as physiological metabolic incompatibility and potential viral transmission. In recent years, with the development of tools such as CRISPR/Cas, precise multi-gene editing technology has become possible, enabling the simultaneous knockout of multiple xenoantigen genes (such as GGTA1, CMAH, and B4GALNT2) and the introduction of human genes regulating complement, coagulation, and immune responses (such as hCD55, hTBM (THBD), and hCD47), significantly improving the immune tolerance and physiological compatibility of donor organs. This article systematically reviews the immune and coagulation barriers in xenotransplantation, focusing on precise multi-gene editing strategies for pigs used in xenotransplantation. It highlights editing pathways such as tandem knock-in at the same site, simultaneous multi-site editing, stepwise modular editing, and homology-directed repair (HDR) enrichment. Combined with representative organ-specific examples (heart, kidney, liver, and lung), including key non-human primate studies and early human exploratory cases where available, it explores the application prospects of these strategies in creating safe clinical-grade donor pigs and promoting the clinical translation of xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 2","pages":"e70128"},"PeriodicalIF":3.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723796","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 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":3.8,"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":"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":3.8,"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":3.8,"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":"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":3.8,"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":3.8,"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}