Xenotransplantation最新文献

{"title":"From Multi-Omics Signatures to Mechanism in Liver Xenotransplantation.","authors":"Lisha Mou, Zuhui Pu","doi":"10.1111/xen.70179","DOIUrl":"https://doi.org/10.1111/xen.70179","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149325135","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":"Corneal Xenotransplantation: Lessons From Allograft Immunobiology and Emerging Translational Strategies.","authors":"Ansu A John, Ellen H Koo","doi":"10.1111/xen.70177","DOIUrl":"10.1111/xen.70177","url":null,"abstract":"<p><p>Corneal transplantation is an effective sight-restoring procedure, yet its global impact remains constrained by limited and uneven access to human donor tissue and by immune-mediated graft failure, particularly in high-risk recipients. Xenotransplantation offers a potentially scalable alternative, but successful clinical translation requires an understanding of how xenogeneic immune responses differ from, and build upon, the mechanisms governing corneal allograft rejection. This review critically examines the immunologic lessons from corneal allotransplantation that are most relevant to xenograft development and evaluates current evidence for porcine corneal xenotransplantation. We focus on the conditional nature of corneal immune privilege, antigen-recognition pathways, and the relationship between donor tissue burden and immune exposure. Particular emphasis is placed on fresh cellular porcine corneal xenotransplantation and non-human primate studies, which demonstrate that prolonged graft survival is achievable but remains dependent on control of T-cell responses, antibody production, complement activation, and macrophage-mediated injury. Porcine corneal xenoantigens, including α-Gal and non-Gal epitopes, further distinguish xenogeneic from allogeneic transplantation. Emerging strategies include genetically engineered donor pigs, targeted immunosuppression and costimulation blockade, tissue-selective lamellar and endothelial xenografts, and decellularized or hybrid constructs designed to reduce xenogeneic antigenic burden. Collectively, current evidence suggests that clinical corneal xenotransplantation is unlikely to depend on a single strategy. Rather, durable and scalable graft survival will likely require an indication-specific combination of donor modification, immune modulation, and graft design. Lessons from corneal allotransplantation therefore provide an important framework for determining which immune barriers can be reduced through tissue selection and which remain unique to the cross-species setting.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13732095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149325134","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 Optimal Site for Pig Islet Xenotransplantation.","authors":"Bottino R, Burdorf L, Terashita M, Kinoshita K, Maenaka A, Cooper Dkc","doi":"10.1111/xen.70172","DOIUrl":"https://doi.org/10.1111/xen.70172","url":null,"abstract":"","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149343674","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":"Blastocyst Complementation: The New Kid on the Xenotransplantation Block.","authors":"Mark B Nottle, Peter J Cowan, Wayne J Hawthorne","doi":"10.1111/xen.70165","DOIUrl":"10.1111/xen.70165","url":null,"abstract":"<p><p>The transplantation of genetically modified pig organs and tissues is arguably the most promising approach to overcoming the world-wide shortage of organ and tissues for transplantation. The advent of gene editing has seen a resurgence in interest in this approach which has also allowed blastocyst complementation to be explored as an alternative to solving this challenge. Genetic strategies are increasingly being used to explore this possibility and overcome the many scientific hurdles this presents. While blastocyst complementation faces many scientific challenges the ethical questions surrounding this approach are equally important and will need to be addressed at the same time, if this new kid on the xenotransplantation block is to become a reality.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70165"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901053","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":"Quantification of Islet Cell Cluster Size Heterogeneity in Early Postnatal Porcine Pancreas.","authors":"Daviana Munoz Cruz, Johanna Frick, Michel Adamina, Léo Bühler, Carmen Gonelle-Gispert","doi":"10.1111/xen.70164","DOIUrl":"10.1111/xen.70164","url":null,"abstract":"<p><p>Donor scarcity limits islet transplantation for type 1 diabetes. Early postnatal piglets are a potential xenogeneic source of endocrine tissue, yet their immature islet cell clusters (ICCs) remain insufficiently characterised with respect to size and maturation. Here, we quantified ICC size heterogeneity in pancreata from six 14-day-old piglets using insulin and glucagon immunofluorescence staining and large-area immunofluorescence imaging with automated whole-section analysis. ICCs were classified as small (1-2 endocrine cells), intermediate (3-5 endocrine cells), or large (≥6 endocrine cells). Well-developed ICCs reaching ∼100 µm in diameter were consistently identified in all animals and exhibited an intermingled β- and α-cell cytoarchitecture similar to that of adult pig and human islets. The densities of small, intermediate, and large clusters were largely comparable among littermates and across piglets, suggesting a consistent distribution of ICC size classes at this postnatal age. Quantitative composition analysis revealed a strong predominance of insulin-positive area. In small and intermediate ICCs, we observed mean β/α cell ratios of 3.7 ± 0.4 and 3.8 ± 0.4, respectively. In large ICCs, the proportion of glucagon staining was significantly higher, decreasing the β/α cell ratio to 2.2 ± 0.3. Together, these data point to a reproducible distribution of ICC sizes in 14-day-old piglet pancreata, including a population of morphologically well-developed, ∼100 µm-sized clusters. These findings from native pancreatic tissue provide a morphological basis for further evaluating 14-day-old piglets as a potential donor source for xenogeneic islet transplantation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70164"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913446","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":"Attitudes Toward Xenotransplantation Among Kidney Transplant Recipients, Candidates, and Living Donors: A Cross-Sectional Survey in Japan.","authors":"Kazuya Kinoshita, Satoshi Nakamura, Takuma Sasaki, Tenshi Makiyama, Akane Morimoto, Masaya Yokoyama, Michihiro Maruyama","doi":"10.1111/xen.70174","DOIUrl":"https://doi.org/10.1111/xen.70174","url":null,"abstract":"<p><strong>Background: </strong>Genetically engineered pig kidneys have entered early clinical use, but attitudes among kidney transplant-related individuals remain poorly characterized.</p><p><strong>Methods: </strong>In this preliminary, exploratory, single-center cross-sectional survey, 101 consecutive eligible adults attending a kidney transplant clinic were approached, and 100 kidney transplant candidates, recipients, and living donors completed a paper, self-administered questionnaire (99.0% participation). We descriptively assessed acceptability, conditions for acceptance, and preferred kidney source. Group comparisons and analyses of factors associated with acceptance were exploratory secondary analyses.</p><p><strong>Results: </strong>Overall, 79.0% (95% CI, 70.0%-85.8%) were accepting of xenotransplantation: 27.0% were willing and 52.0% were conditionally willing. Among conditionally willing participants, 82.7% required assurance of safety and 63.5% required long-term outcome data. Among 87 participants who ranked kidney sources, only 6.9% ranked a pig kidney first and 64.4% ranked it last. Acceptance rates were similar among candidates, recipients, and donors in exploratory comparisons. Physician-related trust was associated with acceptance in exploratory analyses, but interpretation was limited by conceptual overlap between the trust and acceptance items.</p><p><strong>Conclusion: </strong>In this preliminary survey, acceptance of xenotransplantation was high but predominantly conditional, and a pig kidney was rarely preferred. Larger multicenter studies are needed to confirm the exploratory secondary findings.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70174"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184686","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 by Porcine Endothelium Attenuates Thrombus Formation and Platelet Activation in a Dynamic Shear Flow Model.","authors":"Megan Dufault, Sayed-Amir Sanatkar, Zahra Habibabady, Victoria Diaz, Jonathan Schulz, Cinthia Gomes Lucas, Kevin D Wells, Kristin M Whitworth, David Ayares, Richard N Pierson","doi":"10.1111/xen.70176","DOIUrl":"https://doi.org/10.1111/xen.70176","url":null,"abstract":"<p><p>Long term xenografts often fail in association with evidence of coagulation pathway dysregulation, which may be caused in part by the inefficient binding of inactivated protein C (PC) to porcine thrombomodulin (TBM). This study evaluates the effect of human TBM (hTBM) expression by genetically modified pig endothelium on human platelet activation, adhesion, and aggregation within a dynamic in vitro xenoperfusion model. Porcine aortic endothelial cells (PAECs) with a variety of genetic modifications and immortalized human coronary endothelial cells (HCECs) (n = 9) were cultured to confluence in microfluidic channels and perfused for one hour with human whole blood stained with 0.5 mM Calcein to visualize thrombosis formation. After one hour of perfusion, platelet adhesion (as percent surface area coverage) and aggregation (fluorescence intensity) were significantly reduced in association with human APC (hAPC) pretreatment of GTKO, and with DKO.hCD55.hTBM or 10-GE ECs relative to GT/DKO ± hCD55 ECs. Fold change in frequency of activated (CD62P+) platelets in channel effluent was significantly decreased in association with GTKO+hAPC (1.5 ± 0.03 p = 0.01, n = 6), and DKO.hCD55.hTBM (1.6 ± 0.03 p = 0.02, n = 12) or 10-GE ECs (1.3 ± 0.04 p < 0.0001, n = 9) relative to GT/DKO ± hCD55 ECs (1.8 ± 0.07, n = 8). No significant difference was observed between DKO.hCD55.hTBM and GTKO+hAPC. We conclude that, under conditions mimicking microcirculatory flow, hTBM expression confers anti-thrombotic effects comparable to those with hAPC pretreatment of GTKO ECs. Consequently, hTBM expression is a promising method to inhibit platelet dysregulation in xenotransplant models.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70176"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149184677","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":"C-Reactive Protein as a Biomarker of Inflammation and Graft Injury After Kidney and Heart Allo- and Xenotransplantation Into Non-Human Primates.","authors":"Tjasa Zaletel, Gabriela F Elias, Zahra Habibabady, Megan Dufault, Kohei Kinoshita, Ryo Otsuka, Kasinath Kuravi, David Ayares, Kristin M Whitworth, Katherine Hall, Tatsuo Kawai, Joren C Madsen, David K C Cooper, Richard N Pierson","doi":"10.1111/xen.70168","DOIUrl":"10.1111/xen.70168","url":null,"abstract":"<p><strong>Introduction: </strong>C-reactive protein (CRP) is a widely used inflammatory biomarker. We evaluated CRP alongside tissue injury markers in non-human primate (NHP) models of kidney and heart allo- and xeno-transplantation to assess CRP's sensitivity in detecting graft-specific inflammatory responses (acute rejection), and explored CRP elevations in the absence of clinically evident graft injury. A secondary objective compared CRP dynamics between NHP species.</p><p><strong>Methods: </strong>Forty-two baboon or cynomolgus monkey NHPs received kidney (n = 12) or heart (n = 7) xenografts, or kidney (n = 12) or heart (n = 11) allografts. In serum obtained before transplant, after graft revascularization on the day of transplant, and at defined post-operative intervals, CRP, creatinine (kidney), and troponin-I (heart) were measured and correlated with clinical events and histopathology.</p><p><strong>Results: </strong>Baboons exhibited higher baseline and pre-transplant CRP levels than cynomolgus monkeys (p < 0.05). Following kidney xenotransplantation, CRP rose to higher levels in baboons than cynomolgus monkeys (p < 0.05). In association with episodes of histologically confirmed graft rejection, CRP elevations preceded rises in creatinine (kidney) or troponin-I (heart) by 7-14 days. Additionally, CRP elaboration was observed in association with opportunistic infection and surgical procedures such as graft biopsies.</p><p><strong>Conclusion: </strong>As reflected by CRP dynamics, systemic inflammation is associated with organ allo- and xenotransplantation in NHPs. We conclude that CRP is a potentially valuable marker of inflammation that, when interpreted alongside organ-specific biomarkers, quantifies the severity of immune activation associated with graft injury and detects additional inflammatory events, which may be clinically occult but influence experimental outcomes. CRP could be a valuable biometric adjunct in multi-parametric inflammation monitoring in transplantation and other disease models.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70168"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983589","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":"Reference Composition Biases Automated Cell Annotation and Obscures Biological Signals in Xenotransplantation Single-cell Atlases.","authors":"Lisha Mou, Ying Lu, Zijing Wu, Qishan Zhang, Zuhui Pu","doi":"10.1111/xen.70171","DOIUrl":"https://doi.org/10.1111/xen.70171","url":null,"abstract":"<p><p>Artificial intelligence is transforming single-cell biology, but automated annotation depends not only on model architecture but also on reference composition. Whether compositional biases within reference datasets influence AI-assisted cell identity assignment remains poorly understood. Here, we establish a harmonized single-cell resource integrating 254 245 cells from five datasets of genetically engineered pig kidney grafts in human and non-human primate (NHP) recipients. We evaluate representative annotation strategies, including the foundation model TranscriptFormer, the autonomous biomedical agent Biomni, and conventional approaches. Across frameworks, reference composition, represented as the empirical cell-type composition, emerged as a major factor associated with inferred cell identity. In donor-pig kidney grafts, abundant collecting-duct (CD) references promoted widespread CD assignment and suppressed distal tubular identities. Under the empirical reference composition, 97.0% of cells carrying target-native thick ascending limb (TAL) annotations and 97.2% of cells carrying target-native distal convoluted tubule (DCT) annotations in a primary pig-to-NHP kidney xenograft dataset were reassigned to the CD compartment, revealing profound reference-driven label collapse. This distortion extended to compartment-level analyses, obscuring biological programs. Notably, an endothelial interferon-stimulated gene signature in the primary target remained detectable under target-native annotation but was masked by reference-driven label transfer. We establish a harmonized xenotransplantation single-cell resource and identify reference-composition auditing as a general framework for evaluating AI-assisted biological interpretation.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70171"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115249","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":"Ex Vivo Therapeutics in Cardiac Xenotransplantation: A Scoping Review.","authors":"Duc M Giao, Pedro A Catarino, Dominic Emerson, Kambiz Ghafourian, Jon Kobashigawa, Fardad Esmailian, Joanna Chikwe, Laura DiChiacchio","doi":"10.1111/xen.70173","DOIUrl":"10.1111/xen.70173","url":null,"abstract":"<p><p>Genetically modified porcine hearts through xenotransplantation offer a promising solution for the current donor scarcity from human allotransplantation. Machine perfusion has successfully been used for graft preservation in two landmark in-human cardiac xenotransplantation cases using hypothermic oxygenated perfusion. Alternate machine perfusion approaches, including normothermic perfusion on a \"beating heart\" device such as the Transmedics Organ Care System (OCS), have not been fully evaluated. Although preclinical studies have shown that continuous machine perfusion enhances graft viability and function in pig-to-primate cardiac xenotransplantation models, therapeutic questions and challenges remain. We performed a scoping review to assess the current literature and outstanding areas of investigation regarding machine perfusion of cardiac xenografts focusing on the potential for ex vivo therapeutics in this field.</p>","PeriodicalId":23866,"journal":{"name":"Xenotransplantation","volume":"33 5","pages":"e70173"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168586","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}