Frontiers in transplantation最新文献

{"title":"Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 1: their emergence from injuries to the donor organ.","authors":"Walter G Land, Andreas Linkermann","doi":"10.3389/frtra.2025.1571516","DOIUrl":"https://doi.org/10.3389/frtra.2025.1571516","url":null,"abstract":"<p><p>This Part 1 of a bipartite review commences with a succinct exposition of innate alloimmunity in light of the danger/injury hypothesis in Immunology. The model posits that an alloimmune response, along with the presentation of alloantigens, is driven by DAMPs released from various forms of regulated cell death (RCD) induced by any severe injury to the donor or the donor organ, respectively. To provide a strong foundation for this review, which examines RCD and DAMPs as biomarkers and therapeutic targets in normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) to improve outcomes in organ transplantation, key insights are presented on the nature, classification, and functions of DAMPs, as well as the signaling mechanisms of RCD pathways, including ferroptosis, necroptosis, pyroptosis, and NETosis. Subsequently, a comprehensive discussion is provided on major periods of injuries to the donor or donor organs that are associated with the induction of RCD and DAMPs and precede the onset of the innate alloimmune response in recipients. These periods of injury to donor organs include conditions associated with donation after brain death (DBD) and donation after circulatory death (DCD). Particular emphasis in this discussion is placed on the different origins of RCD-associated DAMPs in DBD and DCD and the different routes they use within the circulatory system to reach potential allografts. The review ends by addressing another particularly critical period of injury to donor organs: their postischemic reperfusion following implantation into the recipient-a decisive factor in determining transplantation outcome. Here, the discussion focuses on mechanisms of ischemia-induced oxidative injury that causes RCD and generates DAMPs, which initiate a robust innate alloimmune response.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1571516"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: ABO-incompatible living donor liver transplantation in a patient with associated Rosai-Dorfman-Destombes disease, first reported case.","authors":"Bhabani Sankar Sahoo, Kausar Makki, Vikas Saini, Piyush Srivastava, Vivek Vij","doi":"10.3389/frtra.2025.1576301","DOIUrl":"https://doi.org/10.3389/frtra.2025.1576301","url":null,"abstract":"<p><p>Rosai-Dorfman-Destombes disease (RDD), a rare histiocytic proliferation, is often associated with lymphadenopathy and extranodal manifestations, including involvement of the liver. We report a unique case of RDD presenting with chronic liver disease (CLD) in a 7-year-old boy, highlighting the association between these conditions. The patient underwent ABO-incompatible living donor liver transplantation (LDLT), a procedure not previously documented in the context of RDD. Successful transplantation was preceded by a desensitization protocol including rituximab and immunoadsorption, and was followed by a satisfactory postoperative course. This case underscores the need for further investigation into the relationship between RDD and CLD and the potential of LDLT as a life-saving treatment option in such complex cases.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1576301"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-clinical xenotransplantation: physiology and pharmacy in human decedent and non-human primate models.","authors":"Douglas J Anderson, Jayme E Locke","doi":"10.3389/frtra.2025.1576549","DOIUrl":"https://doi.org/10.3389/frtra.2025.1576549","url":null,"abstract":"<p><p>Non-human primates and decedent humans have emerged as the two principal translational models in xenotransplantation. Each model has differing advantages and drawbacks. In this manuscript, we will compare and contrast the relative strengths of each model, focusing on the physiologic function of the xenograft in a human decedent or non-human primate. Additionally, we will discuss the pharmacologic agents typically employed in each model, highlighting both the ability of the decedent model to test clinically-relevant medication strategies that may be impossible in non-human primates due to species-specificity.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1576549"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2025: status of cardiac xenotransplantation including preclinical models.","authors":"Guerard W Byrne, Christopher G A McGregor","doi":"10.3389/frtra.2025.1568910","DOIUrl":"https://doi.org/10.3389/frtra.2025.1568910","url":null,"abstract":"<p><p>Xenotransplantation offers an opportunity to radically change the availability of organs for life-saving human transplantation. Great progress has been made in porcine donor genetic engineering to reduce the immunogenicity of pig organs and potentially enhance their resistance to antibody-mediated rejection. There is also growing insight into more effective immune suppression regimens. These advances have improved the duration of cardiac xenograft survival in non-human primates over the last decade and supported the recent approval of the first-in-human clinical use of pig hearts and kidneys for transplantation. This review critically examines preclinical and clinical results in cardiac xenotransplantation. We identify challenges that remain to achieve consistent and durable clinical graft survival. We discuss the relative value of preclinical non-human primate and human decedent transplant models to optimize patient cross-matching, immune suppression, postoperative monitoring, and graft survival.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1568910"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor's therapeutic hypothermia vs. normothermia in kidney transplantation: a meta-analysis of randomized controlled trials.","authors":"Luccas Marcolin Miranda, Pedro Emanuel Carneiro De Lima, Nathalia De Carvalho Dias Miranda, Giovanna Zaniolo Margraf, Juliano Riella","doi":"10.3389/frtra.2025.1564460","DOIUrl":"https://doi.org/10.3389/frtra.2025.1564460","url":null,"abstract":"<p><strong>Introduction: </strong>The shortage of organs remains one of the most challenging global problems nowadays. Donor's therapeutic hypothermia was suggested to decrease kidney delayed graft function (DGF) when compared to normothermia in previous trials, but the role of such intervention is still controversial. To assess this, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) investigating the benefits of donor hypothermia in DGF rate and Graft Failure.</p><p><strong>Methods: </strong>MEDLINE, Embase, and Cochrane databases were systematically searched for studies of deceased organ donors who underwent hypothermia or normothermia prior to kidney transplantation. Statistical analysis was performed using R Studio version 3.6. Heterogeneity was assessed using <i>I</i> ² statistics and a Baujat Plot.</p><p><strong>Results: </strong>Four different RCTs were analyzed, including more than 3,000 recipients. Donor hypothermia was associated with a lower, but not statistically significant, rate of DGF (RR 0.87; 95% CI 0.71-1.08; <i>P</i> = .21) and graft failure (RR 0.70; 95% CI 0.45-1.10; <i>P</i> = .12). When analyzing only expanded criteria donors, a significantly lower rate of DGF was observed in the hypothermia-treated group (RR 0.65; 95% CI 0.47-0.89; <i>P</i> = .008). Sensitivity analysis identified one study as an outlier, probably due to protocol deviation. When excluded from the analysis, a significant reduction in DGF rate was observed among the hypothermia-treated group (RR 0.80; 95% CI 0.67-0.94; <i>P</i> = .007).</p><p><strong>Conclusion: </strong>Our meta-analysis could not find a statistical difference between donor therapeutic hypothermia and normothermia in preventing DGF or Graft Failure. However, these results may be influenced by outliers and the limitations of the included studies. Further research is needed to clarify the role of donor hypothermia in kidney transplantation. If proven beneficial, it could be a promising alternative to sites where preservation techniques are limited, such as low-income countries.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024581665, PROSPERO (CRD42024581665).</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1564460"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current issues of translating clinical xenokidney transplantation, with an emphasis on prevention of rejection.","authors":"Jean Kwun, Joseph M Ladowski, Annette M Jackson, Stuart Knechtle","doi":"10.3389/frtra.2025.1559512","DOIUrl":"https://doi.org/10.3389/frtra.2025.1559512","url":null,"abstract":"","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1559512"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Edmonton to Lantidra and beyond: immunoengineering islet transplantation to cure type 1 diabetes.","authors":"El Hadji Arona Mbaye, Evan A Scott, Jacqueline A Burke","doi":"10.3389/frtra.2025.1514956","DOIUrl":"10.3389/frtra.2025.1514956","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells within pancreatic islets, the specialized endocrine cell clusters of the pancreas. Islet transplantation has emerged as a β cell replacement therapy, involving the infusion of cadaveric islets into a patient's liver through the portal vein. This procedure offers individuals with T1D the potential to restore glucose control, reducing or even eliminating the need for exogenous insulin therapy. However, it does not address the underlying autoimmune condition responsible for T1D. The need for systemic immunosuppression remains the primary barrier to making islet transplantation a more widespread therapy for patients with T1D. Here, we review recent progress in addressing the key limitations of islet transplantation as a viable treatment for T1D. Concerns over systemic immunosuppression arise from its potential to cause severe side effects, including opportunistic infections, malignancies, and toxicity to transplanted islets. Recognizing the risks, the Edmonton protocol (2000) marked a shift away from glucocorticoids to prevent β cell damage specifically. This transition led to the development of combination immunosuppressive therapies and the emergence of less toxic immunosuppressive and anti-inflammatory drugs. More recent advances in islet transplantation derive from islet encapsulation devices, biomaterial platforms releasing immunomodulatory compounds or surface-modified with immune regulating ligands, islet engineering and co-transplantation with accessory cells. While most of the highlighted studies in this review remain at the preclinical stage using mouse and non-human primate models, they hold significant potential for clinical translation if a transdisciplinary research approach is prioritized.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1514956"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrapatient tacrolimus variability is associated with medical nonadherence among pediatric kidney transplant recipients.","authors":"Tara B Gavcovich, Vaka K Sigurjonsdottir, Marissa J DeFreitas, Claudia Serrano, Esther Rivas, Migdalia Jorge, Wacharee Seeherunvong, Chryso Katsoufis, Wendy Glaberson, Melisa Oliva, Adela D Mattiazzi, Carolyn Abitbol, Jayanthi Chandar","doi":"10.3389/frtra.2025.1572928","DOIUrl":"10.3389/frtra.2025.1572928","url":null,"abstract":"<p><strong>Background: </strong>Long-term survival of kidney allografts is limited by multiple factors, including nonadherence. High intrapatient variability in tacrolimus levels (≥30%) is associated with <i>de novo</i> donor-specific antibody (<i>dn</i>DSA) formation, increased risk of rejection and graft loss.</p><p><strong>Methods: </strong>We prospectively analyzed the association between tacrolimus intrapatient variability and nonadherence in pediatric kidney transplant recipients. We derived a composite adherence score from 0 to 3 points based on (1) Basel Assessment of Adherence to Immunosuppressive Medical Scale^©; (2) healthcare team score; and (3) intentionally missed laboratory or clinic visits. A score of 1 or more was considered nonadherent. Tacrolimus 12 h trough levels, patient characteristics and clinical outcomes were collected. Tacrolimus IPV was calculated as the coefficient of variation.</p><p><strong>Results: </strong>The nonadherent group had a significantly higher median tacrolimus intrapatient variability (31%) as compared to the adherent cohort (20%) (<i>p</i> < 0.001.) Tac IPV demonstrated strong predictive performance for adherence (AUC 0.772), with a particularly high sensitivity of 90% at thresholds up to 20%, offering a practical and actionable framework for assessing adherence-related risks in clinical practice.</p><p><strong>Conclusions: </strong>Tacrolimus intrapatient variability may be a useful biomarker to identify nonadherence and high-risk patients, allowing for early interventions to prevent adverse graft outcomes.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1572928"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future of islet transplantation beyond the BLA approval: challenges and opportunities.","authors":"Yong Wang, James McGarrigle, Jenny Cook, Peter Rios, Giovanna La Monica, Yingying Chen, Wei Wei, Jose Oberholzer","doi":"10.3389/frtra.2025.1522409","DOIUrl":"10.3389/frtra.2025.1522409","url":null,"abstract":"<p><p>This opinion paper explores the path forward for islet transplantation as a cell therapy for type 1 diabetes, following the Biologics License Application (BLA) approval. The authors review key challenges and opportunities that lie ahead. After a brief overview of the history of human islet transplantation, the paper examines the FDA's regulatory stance on isolated islet cells and the requirements for obtaining a BLA. The authors discuss the significance of this approval and the critical steps necessary to broaden patient access, such as scaling up production, clinical integration, reimbursement frameworks, post-marketing surveillance, and patient education initiatives. The paper highlights that the approval of LANTIDRA as an allogeneic cell transplant for uncontrolled type 1 diabetes marks the beginning of new chapters in improving islet transplantation. The authors emphasize essential areas for development, including advancements in islet manufacturing, optimization of transplant sites, islet encapsulation, exploration of unlimited cell sources, and gene editing technologies. In conclusion, the future of islet transplantation beyond the BLA approval presents challenges and opportunities. While significant regulatory milestones have been reached, hurdles remain. Innovations in stem cell-derived islets, cell encapsulation, and gene editing show promise in enhancing graft survival, expanding the availability of transplantable cells, and reducing the reliance on immunosuppressive drugs. These advancements could pave the way for more accessible, durable, and personalized diabetes treatments.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1522409"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deceased donor uterus transplantation: religious perceptions.","authors":"Jana Pittman, Brigitte Gerstl, Elena Cavazzoni, Natasha Mireille Rogers, Mianna Lotz, Rebecca Deans","doi":"10.3389/frtra.2025.1536754","DOIUrl":"https://doi.org/10.3389/frtra.2025.1536754","url":null,"abstract":"<p><strong>Background: </strong>Uterus transplant now offers an alternative deceased donation treatment option for women with uterine infertility. Limited research exists on religious opinions that may impact the addition of the uterus to current multi-organ deceased donor programs.</p><p><strong>Objective: </strong>To explore the acceptability of uterus transplantation and deceased uterus donation across different religious groups.</p><p><strong>Design: </strong>A cross-sectional survey of 2,497 participants was conducted between October 2022 and January 2023 in NSW Australia. Australia is a culturally and religiously diverse nation with over 60% of people identifying with a religion, including Christianity (43%), Islam (3.2%), Buddhism (2.7%), Hinduism (2.4%). This survey captured awareness and attitudes towards deceased uterus donation. Descriptive statistics and regression analyses were used to explore factors influencing organ donation and next-of-kin perceptions.</p><p><strong>Results: </strong>A total of 2,497 respondents completed the survey. Christians had greater awareness of organ donation but were less likely to be registered donors, or consent to uterus donation. Those of Hindu faith were less likely to be registered organ donors. Next-of-kin from the Islamic faith were reluctant to consent to organ donation if the donor's pre-death wishes were unknown, and less likely to consent to uterus donation. Participants identifying as Buddhist had a higher awareness of uterus transplantation.</p><p><strong>Conclusion: </strong>Organ donor awareness and consent rates varied across religious groups, including for uterus donation. Differences may stem from varying beliefs about bodily integrity, and reproductive rights, which may influence attitudes toward uterus donation. Tailored culturally and linguistically sensitive educational campaigns should address the unique aspects of uterus donation.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"4 ","pages":"1536754"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}