Transplantation最新文献

{"title":"Expanding Human Breg for Cellular Therapy in Transplantation: Time for Translation.","authors":"Adam McNee, Ananya Kannan, Patrick Jull, Sushma Shankar","doi":"10.1097/TP.0000000000005243","DOIUrl":"10.1097/TP.0000000000005243","url":null,"abstract":"<p><p>Regulatory B cells (Breg) are instrumental in protecting allografts in transplantation. Breg signatures are identified in operationally tolerant human kidney transplant recipients and can predict organ survival and acute rejection. Animal models of transplantation and autoimmunity support the use of Breg as an adoptive cellular therapy. Detailed mechanistic studies have identified multiple signaling pathways utilized by Breg in their induction, expansion, and downstream function. These preclinical studies provide the guiding principles, which will inform protocols by which to expand this crucial immunoregulatory population before clinical use. There is an urgent need for novel therapies to improve long-term transplant outcomes and to minimize immunosuppression-related morbidity including life-threatening infection and cancer. Systematic evaluation of the signals, which drive Breg expansion, will be key to transforming the as of yet unharnessed potential of this potent immunoregulatory cell. In this review, we explore the potential avenues of translating Breg subsets from cell culture at the laboratory bench to cell therapy at the patient's bedside. We will discuss the standardization of Breg phenotypes to aid in precursor population selection and quality control of a Breg-cell therapy product. We will evaluate avenues by which to optimize protocols to drive human Breg expansion to levels sufficient for cellular therapy. Finally, we will examine the steps required in process development including scalable culture systems and quality control measures to deliver a viable Breg-cell therapy product for administration to a transplant recipient.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"926-937"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization and Protection of Kidney Health in Liver Transplant Recipients: Intra- and Postoperative Approaches.","authors":"Muhammad Y Jan, Kavish R Patidar, Marwan S Ghabril, Chandrashekhar A Kubal","doi":"10.1097/TP.0000000000005252","DOIUrl":"10.1097/TP.0000000000005252","url":null,"abstract":"<p><p>Postoperative acute kidney injury after liver transplant (LT) has long-term implications for kidney health. LT recipients are at risk of acute kidney injury due to a number of factors related to the donor liver, intraoperative factors including surgical technique, as well as recipient factors, such as pre-LT kidney function and postoperative complications. This review discusses these factors in detail and their impact on posttransplant kidney function. Long-term risk factors such as calcineurin inhibitors have also been discussed. Additionally, the impact of liver allocation policies on pre- and post-LT kidney health is discussed.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"938-944"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Community Socioeconomic Distress With Waitlist and Survival Outcomes in Liver Transplantation.","authors":"Sara Sakowitz, Syed Shahyan Bakhtiyar, Saad Mallick, Fady Kaldas, Peyman Benharash","doi":"10.1097/TP.0000000000005328","DOIUrl":"10.1097/TP.0000000000005328","url":null,"abstract":"<p><strong>Background: </strong>Despite efforts to ensure equitable access to liver transplantation (LT), significant disparities remain. Although prior literature has considered the effects of patient sex, race, and income, the contemporary impact of community socioeconomic disadvantage on outcomes after waitlisting for LT remains to be elucidated. We sought to evaluate the association of community-level socioeconomic deprivation with survival after waitlisting for LT.</p><p><strong>Methods: </strong>All waitlisted candidates for isolated LT were identified using the 2005-2023 Organ Procurement and Transplantation Network. The previously validated Distressed Communities Index, representing poverty rate, median household income, unemployment, business growth, education level, and housing vacancies, was used to characterize community socioeconomic distress. Zip codes in the highest quintile were classified as the \"distressed\" cohort (others: \"nondistressed\"). Kaplan-Meier and Cox proportional hazard models were applied to assess patient and graft survival. We performed a Fine and Gray competing risk regression to consider the impact of distress on waitlist mortality.</p><p><strong>Results: </strong>Of 169 601 patients, 95 020 (56%) underwent LT and 74 581 (44%) remained on the waitlist. Among transplanted patients, 18 774 (20%) were distressed. After adjustment, distressed faced similar posttransplant survival at 1 y but greater mortality hazard at 5 y (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.04-1.12) and 10 y (HR, 1.09; 95% CI, 1.05-1.12). Considering all waitlisted patients, competing risk analysis demonstrated distressed candidates to face significantly greater cumulative incidence of death/deterioration on the waitlist (HR, 1.07; 95% CI, 1.04-1.11).</p><p><strong>Conclusions: </strong>Community-level socioeconomic inequity is associated with greater waitlist mortality and inferior post-LT survival. Novel interventions are needed to address structural barriers to care and continued inequities in outcomes.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"976-984"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lethal Donation: Do Physicians Cause Death or Preserve Organs in NRP-cDCD?","authors":"Emil J N Busch","doi":"10.1097/TP.0000000000005321","DOIUrl":"10.1097/TP.0000000000005321","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"905-909"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coronary Computed Tomography Angiography in Heart Transplant Patients: Current Insights and Future Directions.","authors":"Britt C J van Dijk, Daniel Bos, Stefan Roest, Alexander Hirsch, Yannick J H J Taverne, Jasper J Brugts, Rudolf A de Boer, Ricardo P J Budde, Olivier C Manintveld","doi":"10.1097/TP.0000000000005266","DOIUrl":"10.1097/TP.0000000000005266","url":null,"abstract":"<p><p>Cardiac allograft vasculopathy (CAV) remains a significant challenge after heart transplantation, necessitating effective surveillance methods. This review centers around the role of coronary computed tomography angiography (CCTA) in CAV surveillance, given its unique capabilities to visualize and quantify CAV in comparison with other imaging modalities, including invasive coronary angiography and intravascular ultrasound. CCTA has shown good diagnostic performance for detecting and monitoring CAV, exemplified by a higher sensitivity and negative predictive value compared with invasive coronary angiography. Additionally, CCTA can provide valuable functional insights with fractional flow reserve integration. An additional, considerable benefit of CCTA is that it allows for the opportunity to assess other imaging markers of cardiometabolic and general health, including coronary artery calcium score, epicardial fat volume, liver fat, vertebral bone density, and lung density, which allows for a comprehensive assessment of the overall health of the patient.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"945-954"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemia/Reperfusion Upregulates Genes Related to PANoptosis in Human Lung Transplants.","authors":"Yajin Zhao, Lubiao Liang, Jamie E Jeon, Shaf Keshavjee, Mingyao Liu","doi":"10.1097/TP.0000000000005268","DOIUrl":"10.1097/TP.0000000000005268","url":null,"abstract":"<p><strong>Background: </strong>Activation of multiple programmed cell death (PCD) pathways has been reported in cellular and animal studies of ischemia/reperfusion injury in lung transplantation. However, the status of these pathways in human lung transplants remains unknown. This study investigates the involvement of PCD pathways and their relationship with inflammation and signaling pathways in human lung transplants.</p><p><strong>Methods: </strong>Transcriptomic analysis was conducted on 54 paired human lung tissue samples at the end of cold preservation time and 2 h after reperfusion, collected between 2008 and 2011. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA were used to examine the activation of genes in 6 PCD pathways. The relationships between PCD pathways and inflammation, as well as signaling pathways, were assessed via single-gene GSEA.</p><p><strong>Results: </strong>GSEA results indicated that apoptosis and necroptosis were significantly upregulated after reperfusion in human lung transplants, whereas the gene sets related to pyroptosis, ferroptosis, autophagy, and cuproptosis were not significantly upregulated. Notably, single-sample GSEA demonstrated an intricate interplay among pyroptosis, apoptosis, and necroptosis, collectively referred to as PANoptosis, which is further supported by enrichment of genes related to PANoptosome, inflammatory response, and nuclear factor-κB and interferon signaling pathways, via single-gene GSEA assays.</p><p><strong>Conclusions: </strong>This study demonstrated the genes of PANoptosis are upregulated in human lung grafts during reperfusion. The discovery of PANoptosis as an underlying mechanism of cell death in human lung grafts implies that effective therapeutics to prevent or reduce PANoptosis may alleviate ischemia/reperfusion injury and improve clinical lung transplant outcomes.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1004-1015"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.","authors":"Ryan Chaban, Ikechukwu Ileka, Kohei Kinoshita, Gannon McGrath, Zahra Habibabady, Madelyn Ma, Victoria Diaz, Akihiro Maenaka, Ivy Rosales, Seth Lederman, Victor Tkachev, Joren C Madsen, Richard N Pierson","doi":"10.1097/TP.0000000000005315","DOIUrl":"10.1097/TP.0000000000005315","url":null,"abstract":"<p><strong>Background: </strong>Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells.</p><p><strong>Methods: </strong>Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors. Induction treatment for donor bone marrow transplantation (BMT) was administered after a 4-mo delay period under TNX-1500 monotherapy. The BMT induction regimen comprised 1 (group 1, G1; n = 3) or 2 (group 2, G2; n = 5) doses of total body irradiation, thymic irradiation, and antithymocyte globulin, followed by 2 (G1) or 5 (G2) weekly doses of αCD2 and 5 weekly treatments with αCD28 and TNX-1500.</p><p><strong>Results: </strong>During the delay period, 1 G1 graft was rejected and 2 (1 in each group) exhibited moderate rejection on protocol biopsy before BMT. Lymphocyte chimerism was seen in 3 of 5 G2 animals and in 1 of 2 G1 recipients. One G1 graft was rejected despite chimerism, whereas the other recipient succumbed to anti-cytomegalovirus treatment. Two G2 monkeys succumbed due to infection (cytomegalovirus, bacteremia) post-BMT and 3 due to posttransplantation lymphoproliferative disease.</p><p><strong>Conclusions: </strong>Intensive costimulation pathway blockade with αCD2, αCD154, and αCD28 promotes lymphocyte chimerism at the cost of high incidence of posttransplantation lymphoproliferative disease and opportunistic infections, preventing assessment of the effectiveness of the regimen to promote alloimmune tolerance.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e287-e296"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing Social Determinants of Health to Achieve Equity in Liver Transplantation: Moving From Identification to Implementation.","authors":"Elizabeth S Aby, Alyson Kaplan","doi":"10.1097/TP.0000000000005352","DOIUrl":"10.1097/TP.0000000000005352","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e266-e267"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ Transplantation in India: INDEED, for the Common Good!","authors":"Mohamed Rela, Ashwin Rammohan, Vivek Kute, Manish R Balwani, Arpita Ray Chaudhury","doi":"10.1097/TP.0000000000005349","DOIUrl":"10.1097/TP.0000000000005349","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e340-e342"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Ex Vivo Lung Perfusion Strategies and Transplantation Outcomes: Insights From the United Network for Organ Sharing Data.","authors":"Amer Alzahrani, Kentaro Noda, Ernest G Chan, John P Ryan, Masashi Furukawa, Chadi A Hage, Pablo G Sanchez","doi":"10.1097/TP.0000000000005259","DOIUrl":"10.1097/TP.0000000000005259","url":null,"abstract":"<p><strong>Background: </strong>Ex vivo lung perfusion (EVLP) can increase the donor pool by allowing high-risk lungs to be further evaluated for transplant. Several EVLP platforms are currently in use. This study examines whether different EVLP platforms have any association with post-transplant outcomes.</p><p><strong>Methods: </strong>The United Network for Organ Sharing registry was queried from February 28, 2018, to March 31, 2024, for adult double lung transplant recipients with EVLP data. EVLP platform was categorized as hospital EVLP, EVLP facility, mobile EVLP, or No EVLP. Recipients of EVLP lungs were statistically matched to recipients of No EVLP lungs on donor characteristics.</p><p><strong>Results: </strong>After matching, the final cohort included 1542 in the No EVLP group and 771 who received EVLP. Lungs placed on EVLP had significantly longer ischemic time than No EVLP ( P  < 0.001). Patients who received EVLP lungs had significantly longer post-transplant length of stay (≥25 d versus 21 d No EVLP, P  < 0.001). Ischemic time (OR = 1.04, P  = 0.008) and being in the ICU at the time of transplant (OR = 2.22, P  < 0.001) were associated with higher rates of primary graft dysfunction (PGD3). After adjusting for hospital status and ischemic time, there was no association between the EVLP modality and PGD3. Subgroup analysis showed that DCD recipients did not have worse short- or long-term outcomes.</p><p><strong>Conclusions: </strong>There is no relationship between EVLP modality, PGD3, and post-transplant survival after matching donor quality and adjusting for ischemic time. Work should continue to focus on reducing ischemic times so EVLP can continue to increase the donor pool while limiting adverse effects.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1016-1025"},"PeriodicalIF":5.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}