Xenotransplantation最新文献

{"title":"Impact of COVID-19 Vaccination and Infection on Anti-Triple-Knockout (TKO) Pig Antibody Production: A Study in Patients With End-Stage Liver Disease and Liver Transplant Recipients.","authors":"Liaoran Wang, Li Zhuang, Tao Li, Hidetaka Hara, David K C Cooper, Jianhang Leng, Dengke Pan, Shusen Zheng, Yi Wang, Xiao Xu, Qiang Wei","doi":"10.1111/xen.70050","DOIUrl":"https://doi.org/10.1111/xen.70050","url":null,"abstract":"<p><p>This study investigates the impact of COVID-19 vaccination, with a focus on inactivated vaccines, on the production of anti-triple-knockout (TKO) pig antibodies, crucial for xenotransplantation. Although it is known that vaccination influences anti-pig antibody production, the specific effects of COVID-19 vaccines, particularly inactivated forms, remain underexplored. We analyzed serum samples from healthy individuals, patients with end-stage liver disease (ESLD), and liver transplant (LT) recipients to assess antibody binding to TKO pig cells. Our findings reveal a significant difference in anti-TKO pig antibody levels among healthy controls, ESLD patients, and LT recipients. A positive correlation was observed between SARS-CoV-2 IgG and anti-TKO pig IgG levels in ESLD patients. Additionally, LT recipients with active COVID-19 infection showed significantly higher levels of anti-TKO pig IgG antibodies. These results suggest that both inactivated COVID-19 vaccination and infection may potentially increase anti-TKO pig antibody production. This underscores the importance of closely monitoring anti-pig antibody levels in potential xenotransplant recipients following COVID-19 vaccination or infection, highlighting the need for further research to optimize xenotransplantation protocols in the post-pandemic era.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70050"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080014","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 Nationwide Assessment of Turkish Society's Knowledge and Attitudes Toward Xenotransplantation.","authors":"Sami Akbulut, Zeynep Kucukakcali, Ali Ozer, Cemil Colak","doi":"10.1111/xen.70048","DOIUrl":"https://doi.org/10.1111/xen.70048","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess public perceptions, awareness, and attitudes toward xenotransplantation (XTx) and organ donation in Turkey by examining the influence of demographic, socioeconomic, and religious factors to identify barriers and facilitators to organ donation and XTx acceptance METHODS: This cross-sectional survey was conducted with 10 650 participants, selected through stratified sampling to ensure national representation. Data collection was performed via Computer-Assisted Personal Interviewing (CAPI), with structured questionnaires designed to evaluate participants' perspectives on organ donation, XTx, and religious influences, and comparisons were made based on age groups, geographical region, sectarian affiliation, education level, belief categories, and economic status.</p><p><strong>Results: </strong>Organ donation rates were low across all demographic groups, with notable differences by geographical region, education level, income, age, and religious beliefs. The highest organ donation rate was in Central Anatolia (0.9%), while Southeastern Anatolia had the lowest (0.0%) (p = 0.014). Higher education (p = 0.001) and income levels (p = 0.01) correlated with greater organ donation support. Younger individuals (18-24 years) were less religiously observant, while older participants (65+) displayed the highest religious adherence (p = 0.022). Acceptance of XTx from halal animals was highest in the Aegean region (43.0%) (p = 0.001) and among participants with lower religious adherence (27.4%) (p = 0.004). Approval for XTx from non-halal animals was significantly lower, particularly among highly religious individuals (23.9%). Awareness of XTx-related studies was lowest among participants aged 65+ (9.4%) (p < 0.001) and highest among Maliki participants (27.3%).</p><p><strong>Conclusion: </strong>This study highlights the influence of demographic, socioeconomic, and religious factors on public attitudes toward organ donation and XTx in Turkey. These findings offer critical insights for policymakers and healthcare professionals to design culturally adaptive strategies that improve organ donation rates and foster XTx acceptance.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70048"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079819","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":"Advances in Subclinical and Clinical Trials and Immunosuppressive Therapies in Xenotransplantation.","authors":"Kai Xing, Yuan Chang, Hao Jia, Jiangping Song","doi":"10.1111/xen.70053","DOIUrl":"https://doi.org/10.1111/xen.70053","url":null,"abstract":"<p><p>Organ transplantation remains the foremost effective intervention for end-stage organ failure. Nevertheless, the scarcity of donors has resulted in prolonged waiting times for countless patients globally. The advent of xenografts presents a promising solution to the organ shortage crisis. Although the utilization of xenografts has a long history, it is only in recent years that breakthroughs in genetically modified pigs have rendered successful xenotransplantation a feasible option. In the past 4 years, numerous subclinical and clinical trials have involved xenotransplantation from genetically modified pigs to humans. However, the outcomes have been disappointing, necessitating a reassessment of basic and preclinical research to address the emerging challenges. Furthermore, immunosuppressive therapies remain essential in xenotransplantation. The range of immunosuppressive agents, encompassing traditional immunosuppressants and monoclonal antibodies such as anti-CD154/CD40 monoclonal antibodies, exhibits considerable diversity. However, the most effective drug combination for achieving optimal efficacy remains elusive. This review will offer a succinct overview of the results from recent clinical and subclinical xenotransplantation trials. Moreover, it will highlight recent advancements in immunosuppressive strategies and discuss potential future research directions in this field.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70053"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094245","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":"Humoral Barrier to Preclinical and Clinical Xenotransplantation.","authors":"A Joseph Tector, Matt Tector, Sabrina Copsel, Zhang Yu Wang, Chris Burlak, Luz M Reyes, Jose L Estrada, Victor Novara Gennuso, Andrew B Adams","doi":"10.1111/xen.70056","DOIUrl":"https://doi.org/10.1111/xen.70056","url":null,"abstract":"<p><p>Xenotransplantation is finally moving toward clinical application. Despite the progress in survival in preclinical models and the limited attempts at clinical heart transplantation, the initial problem of xenoreactive antibodies in human serum remains a proximal barrier to widespread success in preclinical and clinical settings. Detailed understanding of the pretransplant status of recipients in the preclinical as well as clinical setting is critical to moving the field forward. The differences in the pretransplant donor-specific antibody (DSA) levels in the preclinical and clinical models are outlined so that we can begin to think about the two scenarios in a complementary fashion and facilitate decision making for research priorities and movement into the clinical realm.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70056"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259040","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":"Public Attitudes Toward Xenotransplantation in South Korea: A 2023 Survey Study.","authors":"Hyeonji Jeon, Jungbeen Lee, Ivo Kwon","doi":"10.1111/xen.70051","DOIUrl":"10.1111/xen.70051","url":null,"abstract":"<p><strong>Background: </strong>Xenotransplantation is a promising field to solve the problem of insufficient allograft and has been actively studied in Korea. However, there are a number of ethical, legal, and social issues to consider, and it is necessary to know the public attitudes regarding them.</p><p><strong>Methods: </strong>A Computer Aided Web Interview consisting of 22 questionnaire items was conducted to investigate the attitudes of Korean related to xenotransplantation. Participants were selected from Hankook Research MS (Master Sample) panel. A total of 1007 sets of data were finally collected and analyzed with SPSS. A statistical analysis was performed using an independent t-test and chi-square method.</p><p><strong>Results: </strong>72.9% of the respondents were positive about xenotransplantation, while 22.2% negative. 61.7% said that they would accept xenotransplantation for incurable diseases. 64.4% agreed with genetically modified pigs for organ resource. 61% agreed that the brain dead could be transplanted first for research purpose, while 32.7% disagreed. The ratio of response that the risk of zoonotic infection is important was 97.2%; the safety issue due to immunosuppression 98.7%; the human identity issue after transplantation 67.4%; and the animal right issue 51.6%. Men were more favorable to xenotransplantation than women on all but one item (stigmatization). There was no significant difference between religions except for the human identity issue.</p><p><strong>Conclusion: </strong>Korean people are favorable to xenotransplantation as a therapeutic option and also positive with the use of pig even genetically modified in spite of the issue of animal rights. They are also positive with the idea of using the brain dead as study subject for xenotransplantation, which is currently forbidden in Korea.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70051"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094808","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":"New Hope for the Treatment of Severe Skin Injury: Genetically Engineered Porcine Skin Xenotransplantation.","authors":"Dan Wu, Xian-Sheng Zhao, Hong-Fang Zhao, Jia-Heng Xie, Hong-Jiang Wei, Ning-Wen Zhu","doi":"10.1111/xen.70057","DOIUrl":"10.1111/xen.70057","url":null,"abstract":"<p><p>Treatments of severe skin injuries have long been a clinical challenge. Early excision of necrotic tissue and skin grafting are essential, yet their effectiveness is hampered by several issues. Autologous and allogeneic skin shortages, the high cost of tissue-engineered skin, and its failure to fully mimic natural skin architecture limit treatment options. Porcine skin is the ideal donor for skin xenotransplantation. It closely resembles human skin in anatomical structure and physiological function, has abundant availability, and involves fewer ethical concerns. Gene-editing technologies allow for the genetic modification of pigs, minimizing xenogeneic immune rejection and zoonotic pathogen transmission risks, thus enhancing the scalability of porcine skin xenotransplantation. This article reviews advantages and limitations of porcine skin as a xenogeneic skin graft, along with the latest preclinical and clinical research on porcine skin xenotransplantation, with a particular emphasis on genetically modified pigs. It aims to highlight the significant potential of gene-edited porcine skin xenotransplantation in treating severe skin wounds. Insights from skin xenotransplantation can also serve as a valuable reference for the development of other organ xenotransplantation. Trial Registration: ClinicalTrials.gov identifier: NCT03695939 and NCT06223269.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70057"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128918","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":"Construction and Validation of a Predictive Model for the Acceptance of Kidney Xenotransplantation by Medical Staff.","authors":"Shujun Yang, Hao Wei, Jiang Peng, Shengkun Sun, Panfeng Shang","doi":"10.1111/xen.70054","DOIUrl":"https://doi.org/10.1111/xen.70054","url":null,"abstract":"<p><p>With gene editing technology and immunosuppressive drugs, kidney xenotransplantation has developed rapidly in recent years. However, as the most cutting-edge medical personnel, there are few reports on the acceptance and awareness of kidney xenotransplantation. This study conducted an online questionnaire survey on medical staff and constructed the first predictive model for the acceptance of kidney xenotransplantation by medical staff through univariate and multivariate analysis of each variable. Their acceptance rate is 72.8%, and it was found that the willingness to donate organs, awareness of kidney xenotransplantation, and residential areas are independent factors affecting their acceptance rate. In addition, the study also found that although healthcare workers have a high acceptance and willingness to share, their awareness of kidney xenotransplantation is relatively low. This reminds us that in order to increase public acceptance of xenotransplantation, the first step is to start with promoting xenotransplantation among medical personnel.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70054"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259038","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":"Anatomical and Physiological Considerations for Pig Cardiac Xenotransplantation.","authors":"M Flowers, S Paika, D K C Cooper, H N Mayrovitz","doi":"10.1111/xen.70049","DOIUrl":"https://doi.org/10.1111/xen.70049","url":null,"abstract":"<p><p>The escalating incidence of heart failure globally, and in the United States, necessitates innovative solutions beyond conventional human cardiac transplantation due to donor heart shortage. Recent measures to overcome this shortage include the novel idea of cardiac xenotransplantation, with the first procedure done in January 2022 at the University of Maryland. However, the patient did not survive in the postoperative phase, highlighting potential challenges in cardiac xenotransplantation. Trace amounts of research exist on the physiological impacts subsequent to innate anatomical differences of porcine hearts, regardless of genetic modifications in growth rates. As such, this review aims to explore and address the critical implications of utilizing genetically modified porcine hearts for cardiac xenotransplantation as it pertains to postoperative physiological function. An analysis of literature discussing multiple anatomical and physiological factors, such as differences in organ dimensions, vasculature, and cardiac conduction, was carried out. Although xenotransplantation offers a promising solution, the present analysis of relevant literature points out potentially important considerations relating to long-term survivability.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70049"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094807","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 CD55 Expression and C1 Inhibition Partially Protect Gene-Edited Pig Red Blood Cells From Human Complement-Mediated Hemolysis In Vitro.","authors":"Akihiro Maenaka, Maho Terashita, Kohei Kinoshita, David K C Cooper","doi":"10.1111/xen.70060","DOIUrl":"https://doi.org/10.1111/xen.70060","url":null,"abstract":"<p><strong>Background: </strong>In recent years, gene-edited pigs have become sources of organs for clinical xenotransplantation. They have the potential to be sustainable sources of red blood cells (pRBCs). We investigated in vitro the effect of human complement inhibition by using (i) human CD55-expressing pRBCs from pigs with 10 gene-edits (10GE) and (ii) a C1-esterase inhibitor (C1-INH).</p><p><strong>Methods: </strong>RBCs were collected from pigs (triple-knockout [TKO] with or without expression of \"protective\" human transgenes [10GE] on peripheral blood mononuclear cells [PBMCs], including two complement-regulatory proteins, hCD46 and hCD55). hCD46 and hCD55 expression, anti-pRBC antibody binding, and C3b/iC3b deposition were measured by flow cytometry. Hemolysis by complement-dependent cytotoxicity (CDC) was measured by a plate reader. A C1-INH was added to the hemolysis assay.</p><p><strong>Results: </strong>HCD46 was not expressed on either TKO or 10GE pRBCs. hCD55 was expressed at low levels on 10GE pRBCs. Hemolysis induced by human complement and anti-pRBC antibodies was less when pRBCs were from 10GE pigs than from TKO pigs (57.3% ± 2.2% vs. 26.2% ± 3.8%, p < 0.01). C3b/iC3b deposition of 10GE pRBCs under nonhemolytic conditions was also lower. C1-INH decreased hemolysis (No C1-INH = 18.6% ± 2.3% vs. 2.5U/mL C1-INH = 7.0% ± 1.1%, p < 0.05). C3b/iC3b deposition on pRBCs was also decreased (gMFI: No C1-INH = 2680 ± 82 vs. 2.5 U/mL C1-INH = 719 ± 57, p < 0.01).</p><p><strong>Conclusions: </strong>Even low expression of hCD55 contributes to the protection of pRBCs from hemolysis by CDC, but the possibility of phagocytosis still remains. However, C1-INH partially protects pRBCs from hemolysis and C3b/iC3b deposition. Therefore, higher hCD55 expression and the administration of a complement inhibitor are likely to prolong pRBC survival after clinical xenotransfusion.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70060"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259039","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":"Quantitative Proteomic Analysis of Cardiac Xenograft Failure in a Pig-to-Non-Human Primate Model Identifies NF-κB as a Critical Immunomodulatory Target.","authors":"Hao Cui, Zirui Liu, Songren Shu, Xin Yan, Xiumeng Hua, Yuan Chang, Xiao Chen, Menghao Tao, Mingming Su, Mengxia Fu, Shengshou Hu, Jiangping Song","doi":"10.1111/xen.70040","DOIUrl":"10.1111/xen.70040","url":null,"abstract":"<p><strong>Introduction: </strong>Shortage of donor organs is one of the greatest challenges of cardiac transplantation. Xenotransplantation is a potential way to solve the contradiction of imbalance and pigs are considered ideal donor sources. However, xenotransplantation still faces the problem of immune rejection at present. In order to further understand the molecular picture of immune rejection after xenotransplantation, and develop immunosuppressive agents to further overcome rejection, we conducted a proteomic analysis of a heterotopic pig-to-non-human primate (NHP) animal model.</p><p><strong>Methods: </strong>We constructed a heterotopic NHP animal model using wild-type (WT) and alpha-1,3-galactosyltransferase gene knockout (GTKO) porcine hearts as donors. Based on quantitative proteomics analysis, we investigated the changes of protein after CXTx in three groups: Group I: WT donor heart, Group II: GTKO donor heart without immunosuppression, and Group III: GTKO donor heart with immunosuppression. Finally, we assessed the efficacy of the target using a heterotopic heart transplantation model from SD rats to Balb/c mice.</p><p><strong>Results: </strong>A total of 2425 proteins were identified in the donor heart tissues and approximately 15% of proteins were significantly changed after CXTx, most of them had increased expression. The results of proteomic analysis demonstrated that chronic hypoxia injury induced by microvascular thrombosis may play an important role during cardiac xenograft failure, confirmed by histopathological results. Remarkably, we showed some novel targets especially increased expression of pentraxin 3, MVP, and HSP90AB1 that cannot be suppressed in the present gene editing and immunosuppressive interventions. Because NF-κB is a common downstream regulator of these three proteins, we hypothesize that it may be crucial to the occurrence of xenograft failure and considered as a potential therapeutic target. Using the SD Rat-Balb/C Mouse CXTx model and inhibiting NF-κB with BAY 11-7082, we found that NF-κB targeting prolonged graft survival from 5 to 8 days and reduced myocardial inflammation.</p><p><strong>Conclusions: </strong>In summary, the proteomic analysis could help us to solve the mystery of cardiac xenograft failure, confirm the key pathways, and reveal a clear vision of future interventions. NF-κB inhibition effectively decreased immune cell infiltration and antibody deposition in myocardial tissue, suggesting its potential as a therapeutic strategy to enhance graft survival and reduce inflammation in cardiac xenotransplantation (CXTx).</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 3","pages":"e70040"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080125","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}