Pranjal Kashiv, Manish Balwani, Amit Pasari, Vivek B Kute, Shubham Dubey
{"title":"Initiating Xenotransplantation in India: Foundations, Challenges, and the Road Ahead.","authors":"Pranjal Kashiv, Manish Balwani, Amit Pasari, Vivek B Kute, Shubham Dubey","doi":"10.1111/xen.70078","DOIUrl":"https://doi.org/10.1111/xen.70078","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 5","pages":"e70078"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126326","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":"Assessment of Porcine Endogenous Retrovirus Infectivity to Human Cells Using Flowcytometric Isolation After Co-Culture.","authors":"Hiroto Miura, Haruka Uryu, Shodai Ishikawa, Takamitsu Tsukahara, Hiroshi Nagashima, Ryo Inoue","doi":"10.1111/xen.70073","DOIUrl":"10.1111/xen.70073","url":null,"abstract":"<p><p>Pigs have been utilized as the donor animal for xenotransplantation, a promising solution to the continued shortage of organ donor. However, porcine endogenous retrovirus (PERV), a gamma retrovirus present in all pig genomes, remains a major concern for the microbiological safety of donor pigs. Therefore, accurately assessing the risk of PERV infection is essential for the clinical application of xenotransplantation. To improve the evaluation of PERV infectivity, here we developed a new in vitro co-culture method for porcine and human cells, applying flowcytometric cell sorter for specific isolation of human cells. This method allows direct contact between porcine and human cells without special treatment that would affect PERV replication, which is better simulating the situation observed in in vivo xenotransplantation. Using this method, we identified several possible factors affecting PERV infectivity, including the period during which porcine and human cells are in contact, the number of porcine cells used, and the levels of PERV mRNA expression in porcine cells. Notably, we found that the PERV infection of human cells can occur within the first 24 h of contact if porcine cells are of a high-risk type for PERV infection, which is not confirmed by any types of conventional co-culture methods. Our result emphasized the importance of selecting appropriate donor pigs with lower risk of PERV infection. Our newly developed method may help the testing and selection of pigs with lower risk of PERV infection.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 5","pages":"e70073"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065687","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":"Addressing Racial Disparities in Xenotransplantation Acceptance: A Call for Deeper Societal Understanding.","authors":"Luz A Padilla, Daniel J Hurst","doi":"10.1111/xen.70079","DOIUrl":"https://doi.org/10.1111/xen.70079","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 5","pages":"e70079"},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081737","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}
Kasra Shirini, Joseph M Ladowski, Raphael P H Meier
{"title":"Xenotransplantation Literature Update: January-June 2025.","authors":"Kasra Shirini, Joseph M Ladowski, Raphael P H Meier","doi":"10.1111/xen.70072","DOIUrl":"10.1111/xen.70072","url":null,"abstract":"<p><p>From January to June 2025, the field of xenotransplantation progressed rapidly toward clinical translation, with landmark compassionate-use cases, peer-reviewed reports of porcine kidney, heart, and liver transplants in humans, and the release of authoritative international guidelines. This literature update summarizes key developments across clinical trials, immunological insights, donor engineering, preservation strategies, infection control, and ethical frameworks, highlighting a growing consensus on the scientific and regulatory roadmap for safe, effective, and equitable xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70072"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144971530","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}
Daniel Rodger, Luz A Padilla, Daniel J Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos
{"title":"Pilot Survey of Attitudes Toward Xenotransplantation Among Nursing Students in London, UK.","authors":"Daniel Rodger, Luz A Padilla, Daniel J Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos","doi":"10.1111/xen.70063","DOIUrl":"10.1111/xen.70063","url":null,"abstract":"<p><strong>Background: </strong>Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.</p><p><strong>Methods: </strong>A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was reviewed and approved by the university research ethics panel.</p><p><strong>Results: </strong>Fifty-two percent of students viewed xenotransplantation positively when the risks and outcomes were equal to allotransplantation. Students were most positive toward accepting a liver from an animal source and the most negative toward accepting a heart. There was limited concern about the potential psychosocial effects of xenotransplantation. Students believed that xenotransplantation involved several risks, including immunologic, infection, and raising religious, ethical, and philosophical problems.</p><p><strong>Conclusion: </strong>While participants had a moderately positive view toward xenotransplantation when the risks and outcomes were equal to allotransplantation-this dropped significantly if it produced worse outcomes. Their primary concerns about xenotransplantation were its potential infection risks as well as the ethical, philosophical, and religious problems it raises. The fact that the source organs are genetically engineered made students view xenotransplantation more favorably.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70063"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529883","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}
Nicola Pradegan, Annamaria Tolomeo, Diego Ciccarelli, Emanuele Cozzi, Antonio Vitiello, Andrea Zovi, Gino Gerosa
{"title":"Immunosuppressive and Non-Immunosuppressive Drugs for Heart Xenotransplantation in Humans: Is Europe Ready?","authors":"Nicola Pradegan, Annamaria Tolomeo, Diego Ciccarelli, Emanuele Cozzi, Antonio Vitiello, Andrea Zovi, Gino Gerosa","doi":"10.1111/xen.70061","DOIUrl":"10.1111/xen.70061","url":null,"abstract":"<p><p>Xenotransplantation is becoming an emerging field of interest for the treatment of end-stage heart disease. In fact, the shortage of human heart donors in European countries requires the increasing investigation of alternative strategies such as heart xenotransplantation. Among different limitations in this peculiar field, the experimental pharmacological management of patients who undergo heart xenotransplantation is primarily narrowed by the indications for which these drugs have been previously authorized by international medicines agencies. In fact, many of these medications have been never authorized for transplant rejection therapy, or for xenotransplantation, but their mechanism of action might stop the molecular pathways which are involved in xenograft antibody-mediated rejection. Additionally, drugs costs and supply can restrict their availability for xenotransplantation practice. The aim of this review is to describe the current drugs which have been used in the clinical cases of heart xenotransplantation performed to date, to analyze the indications for which they are authorized, and to evaluate the future medications which might be implemented in heart xenotransplantation field, with a particular focus on the European scenario.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70061"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529881","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":"RETRACTION: An IgM Cleaving Enzyme for Clearance of Anti-Pig Xenoreactive Antibodies in a Nonhuman Primate Model.","authors":"","doi":"10.1111/xen.70070","DOIUrl":"10.1111/xen.70070","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70070"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875471","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":"RETRACTION: Combinatorial Decellularization as a Better Approach to Porcine Liver Extracellular Matrix Scaffold Fabrication with Preserved Bioactivity: A Comparative Evaluation.","authors":"","doi":"10.1111/xen.70069","DOIUrl":"10.1111/xen.70069","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70069"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875472","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}
Tianyi Hu, Hao Feng, Man Zhang, Jiaxiang Du, Yahui Huang, Jiang Zhang, Song Chen, Dengke Pan, Lan Zhu, Gang Chen
{"title":"In Vitro Evaluation of the Inhibitory Effects of Eculizumab and C1 Esterase Inhibitor on Human and Rhesus Monkey Complement.","authors":"Tianyi Hu, Hao Feng, Man Zhang, Jiaxiang Du, Yahui Huang, Jiang Zhang, Song Chen, Dengke Pan, Lan Zhu, Gang Chen","doi":"10.1111/xen.70064","DOIUrl":"10.1111/xen.70064","url":null,"abstract":"<p><strong>Background: </strong>Complement inhibitors are important therapeutic drugs after xenotransplantation. However, it is still unclear whether the commonly used clinical complement inhibitors eculizumab and C1 esterase inhibitor (C1-INH) can effectively inhibit complement activation in nonhuman primates.</p><p><strong>Methods: </strong>The anti-complement activities of eculizumab and C1-INH were evaluated using an in vitro model of normal human serum (NHS) or normal rhesus monkey serum (NRS)-mediated complement-dependent cytotoxicity (CDC), with an immortalized porcine aortic endothelial cell line (iPEC) as the target.</p><p><strong>Results: </strong>Pretreatment of the NHS with various doses of eculizumab potently inhibited the cell lysis of iPECs. FACS analysis showed that eculizumab potently suppressed the deposition of C5b-9, but not C3c and C4c, on iPECs. However, although eculizumab pretreatment of the NRS had a dose-dependent inhibitory effect on the killing of iPECs, the effect was much weaker than that for similarly treated NHS. Pretreatment of NHS and of NRS with C1-INH produced almost identical dose-dependent inhibitory effects on the killing of iPECs. At the highest concentration (10 IU/mL) of C1-INH used, the CDC was reduced by only about 75%. In addition, C1-INH had moderate inhibitory effects on the deposition of C3c, C4c, and C5b-9 in both humans and rhesus monkeys. When C1-INH was given intravenously to rhesus monkeys at a dose of 17.5 IU/kg, the serum-mediated cell lysis detected in vitro was only slightly reduced, and the maximum inhibition was about 20%.</p><p><strong>Conclusion: </strong>The inhibitory effect of eculizumab on human complement was significantly stronger than it was on rhesus monkey complement, showing obvious species specificity. The inhibitory effect of C1-INH on complement in humans and rhesus monkeys was similar, but a higher concentration of C1-INH was required in monkeys to achieve a significant inhibitory effect. These results provide a reference basis for the selection of complement inhibitors after clinical or preclinical xenotransplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"32 4","pages":"e70064"},"PeriodicalIF":4.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529882","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}