Transplant International最新文献_第3页

Contrast-Enhanced Ultrasound to Assess Kidney Quality During Ex Situ Normothermic Machine Perfusion. 非原位恒温机器灌注时对比增强超声评估肾脏质量。

IF 2.7 3区医学

Transplant International Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14268

Samuel J Tingle, Chloe Connelly, Emily K Glover, Ben Stenberg, Andrew McNeill, Georgios Kourounis, Beth G Gibson, Balaji Mahendran, Lucy Bates, Madison N Cooper, Rhys R Pook, Samantha Lee, Marnie L Brown, Rodrigo Figueiredo, Kevin J Marchbank, Simi Ali, Neil S Sheerin, Colin H Wilson, Emily R Thompson

{"title":"Contrast-Enhanced Ultrasound to Assess Kidney Quality During Ex Situ Normothermic Machine Perfusion.","authors":"Samuel J Tingle, Chloe Connelly, Emily K Glover, Ben Stenberg, Andrew McNeill, Georgios Kourounis, Beth G Gibson, Balaji Mahendran, Lucy Bates, Madison N Cooper, Rhys R Pook, Samantha Lee, Marnie L Brown, Rodrigo Figueiredo, Kevin J Marchbank, Simi Ali, Neil S Sheerin, Colin H Wilson, Emily R Thompson","doi":"10.3389/ti.2025.14268","DOIUrl":"https://doi.org/10.3389/ti.2025.14268","url":null,"abstract":"Normothermic machine perfusion (NMP) provides opportunity for viability assessment of donated kidneys. Diminished microvascular perfusion, despite adequate total blood flow, is a key pathophysiology in ischaemia-mediated acute kidney injury. Contrast-enhanced ultrasound (CEUS) could allow objective assessment of microvascular perfusion during renal NMP. Blood-based NMP was performed on porcine kidneys (circulatory death model) and human kidneys declined for transplant (preclinical). CEUS was performed with a contrast bolus into the NMP circuit arterial limb. Microvascular perfusion quality was quantified and z-score normalisation allowed combination of metrics and regions into an overall \"CEUS-score.\" In porcine kidneys, inferior microvascular perfusion of cortex and medulla correlated with increased urinary NGAL (Neutrophil gelatinase-associated lipocalin) and histological DNA-fragmentation (a hallmark of apoptosis). In human kidneys, CEUS-score at 2 h was correlated with histological DNA-fragmentation (r = -0.937; P = 0.019) and predicted urinary NGAL at 24 h of NMP (r = -0.925; P = 0.024). Total renal flow was not correlated with these outcomes. An open-source web application (stingle.shinyapps.io/Time_intensity_analysis) and R package (\"tican\") were developed for quantitative time-intensity curve analysis. CEUS allows objective point-of-care microvascular perfusion assessment during NMP. As 2-hour CEUS-score predicts NGAL at 24 h, CEUS warrants future clinical investigation as a potential tool to assess kidney quality in assessment and reconditioning centres.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"14268"},"PeriodicalIF":2.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Neurogenin 3 Induction on Endocrine Differentiation and Delamination in Adult Human Pancreatic Ductal Organoids. 神经原素3诱导对成人胰腺导管类器官内分泌分化和分层的影响。

IF 2.7 3区医学

Transplant International Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.13422

Juri Juksar, Rachel Mijdam, Sabine Bosman, Alexander van Oudenaarden, Françoise Carlotti, Eelco J P de Koning

{"title":"Effects of Neurogenin 3 Induction on Endocrine Differentiation and Delamination in Adult Human Pancreatic Ductal Organoids.","authors":"Juri Juksar, Rachel Mijdam, Sabine Bosman, Alexander van Oudenaarden, Françoise Carlotti, Eelco J P de Koning","doi":"10.3389/ti.2025.13422","DOIUrl":"https://doi.org/10.3389/ti.2025.13422","url":null,"abstract":"Diabetes mellitus is characterized by the loss of pancreatic insulin-secreting β-cells in the Islets of Langerhans. Understanding the regenerative potential of human islet cells is relevant in the context of putative restoration of islet function after damage and novel islet cell replacement therapies. Adult human pancreatic tissue can be cultured as three-dimensional organoids with the capacity for long-term expansion and the promise of endocrine cell formation. Here, we characterize the endocrine differentiation potential of human adult pancreatic organoids. Because exocrine-to-endocrine differentiation is dependent on the expression of Neurogenin 3 (NEUROG3), we first generated NEUROG3-inducible organoid lines. We show that doxycycline-induced NEUROG3 expression in the organoids leads to the formation of chromogranin A positive (CHGA+) endocrine progenitor cells. The efficiency of this differentiation was improved with the addition of thyroid hormone T3 and the AXL inhibitor R428. Further, compound screening demonstrated that modifying the pivotal embryonic endocrine pancreas signalling pathways driven by Notch, YAP, and EGFR led to increased NEUROG3 expression in organoids. In a similar fashion to embryonic development, adult ductal cells delaminated from the organoids after NEUROG3 induction. Thus, mechanisms in islet (re)generation including the initiation of endocrine differentiation and delamination can be achieved by NEUROG3 induction.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"13422"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allogeneic Islet Transplantation: Chronicle of a Death Foretold? 异体胰岛移植：死亡预言的编年史？

IF 2.7 3区医学

Transplant International Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14598

Thierry Berney, Olivier Thaunat, Ekaterine Berishvili

{"title":"Allogeneic Islet Transplantation: Chronicle of a Death Foretold?","authors":"Thierry Berney, Olivier Thaunat, Ekaterine Berishvili","doi":"10.3389/ti.2025.14598","DOIUrl":"https://doi.org/10.3389/ti.2025.14598","url":null,"abstract":"Innovative solutions have entered the routine management of patients with type 1 diabetes or are making the headlines and this is shaking the world of beta cell replacement therapies. Above all, allogeneic islet transplantation is enthusiastically doomed to extinction by the aficionados of \"closed loop\" artificial insulin delivery systems or those convinced of the imminent large scale availability of stem-cell derived insulin-producing tissues. This opinion paper will propose that neither will be a universal solution in the very near future and will argue that xenogeneic islet transplantation may be a serious outsider in the race for new therapies. In the meantime, the odds are in favor of allogeneic islet (and pancreas) transplantation remaining first line options in the treatment of complicated type 1 diabetes. There is no question that \"closed loop\" systems have already greatly improved the management of type 1 diabetes, but, while \"unlimited\" sources of insulin-producing cells are jockeying for approval as standard-of-care, these improvements are more likely to drive a shift of indications -from islet transplant alone to simultaneous islet-kidney transplantation- than to herald the demise of islet transplantation.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"14598"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Last Mile in Beta-Cell Replacement Therapy for Type 1 Diabetes: Time to Grow Up. 1型糖尿病β细胞替代疗法的最后一英里：是时候长大了。

IF 2.7 3区医学

Transplant International Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14565

Lorenzo Piemonti

{"title":"The Last Mile in Beta-Cell Replacement Therapy for Type 1 Diabetes: Time to Grow Up.","authors":"Lorenzo Piemonti","doi":"10.3389/ti.2025.14565","DOIUrl":"https://doi.org/10.3389/ti.2025.14565","url":null,"abstract":"Beta cell replacement therapy for type 1 diabetes (T1D) is undergoing a transformative shift, driven by advances in stem cell biology, gene editing, and tissue engineering. While islet transplantation has demonstrated proof-of-concept success in restoring endogenous insulin production, its clinical impact remains limited by donor scarcity, immune rejection, and procedural complexities. The emergence of stem cell-derived beta-like cells represents a paradigm shift, with initial clinical trials showing promising insulin secretion in vivo. However, translating these breakthroughs into scalable, widely accessible treatments poses significant challenges. Drawing parallels to space exploration, this paper argues that while scientific feasibility has been demonstrated, true accessibility remains elusive. Without a strategic shift, beta cell therapy risks becoming an elite intervention, restricted by cost and infrastructure. Lessons from gene and cell therapies for rare diseases highlight the dangers of unsustainable pricing and limited market viability. To bridge the \"last mile\" a Quality by Design approach is proposed, emphasizing scalability, ease of use, and economic feasibility from the outset. By emphasizing practical implementation over academic achievements, corporate interests, market economics, or patent constraints, beta cell therapy can progress from proof-of-concept to a viable, widely accessible treatment.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"14565"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver Transplant for Acute Cholestatic Crisis in Sickle Cell Disease. 肝移植治疗镰状细胞病急性胆汁淤积危重症。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-27 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14086

Sabrina Welland, Jan Christopher Kamp, Björn Hartleben, Richard Taubert, René Abu Isneineh

引用次数: 0

Transplant Trial Watch. 移植试验观察。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-26 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14603

John O'Callaghan, John Fallon

引用次数: 0

Anti-TNFα as an Adjunctive Therapy in Pancreas and Kidney Transplantation. 抗tnf α作为胰腺和肾脏移植的辅助治疗。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-18 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14026

Christophe Masset, Benoit Mesnard, Olivia Rousseau, Alexandre Walencik, Ismaël Chelghaf, Magali Giral, Aurélie Houzet, Gilles Blancho, Jacques Dantal, Julien Branchereau, Claire Garandeau, Diego Cantarovich

{"title":"Anti-TNFα as an Adjunctive Therapy in Pancreas and Kidney Transplantation.","authors":"Christophe Masset, Benoit Mesnard, Olivia Rousseau, Alexandre Walencik, Ismaël Chelghaf, Magali Giral, Aurélie Houzet, Gilles Blancho, Jacques Dantal, Julien Branchereau, Claire Garandeau, Diego Cantarovich","doi":"10.3389/ti.2025.14026","DOIUrl":"10.3389/ti.2025.14026","url":null,"abstract":"The rate of early pancreas allograft failure remains high due to thrombosis but also to severity of rejection episodes. We investigated if adjunct anti-TNFα therapy was safe and could improve outcomes after pancreas transplantation. We investigated all pancreas transplants performed in our institution between 2010 and 2022. Etanercept, an anti TNFα therapy, was added to our standard immunosuppressive regimen since 2017 after approval from our institutional human ethics committee. Pancreas survival, rejection episodes, as well as infectious complications were analyzed. A total of 236 pancreas transplants were included, among whom 87 received Etanercept for induction. In multivariable analysis, after adjustment on confounding variables, pancreas survival did not differ between groups (HR = 0.92, CI 95% = 0.48; 1.73, p = 0.79). However, patients receiving Etanercept presented a significantly lower occurrence of pancreas rejection in multivariate analysis (HR = 0.36, CI 95% = 0.14; 0.95, p = 0.04). Patients receiving Etanercept did not experienced a higher risk of bacterial, fungal, CMV nor BK virus infections compared to the non-treated group. The use of anti-TNFα after pancreas transplantation was safe and did not increase infectious complications. Despite a similar rate of thrombosis, anti-TNFα significantly reduced pancreatic rejection, thus supporting its use among pancreas transplant recipients.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"14026"},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Successful Organ Donation After Yew Intoxication. 红豆杉中毒后成功的器官捐献。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-13 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.13962

P Appelt, A Stuerzebecher, L Weidhase, S Ziganshyna

引用次数: 0

Analysis of Unused Organ Donors in the Netherlands: Older Donor Age Associated With Higher Risk of Non-Utilization. 荷兰未使用器官供者分析：供者年龄越大，未使用的风险越高。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.14157

K A Chotkan, M A Kuiper, I P J Alwayn, M B A Heemskerk, A E Braat, N E Jansen

{"title":"Analysis of Unused Organ Donors in the Netherlands: Older Donor Age Associated With Higher Risk of Non-Utilization.","authors":"K A Chotkan, M A Kuiper, I P J Alwayn, M B A Heemskerk, A E Braat, N E Jansen","doi":"10.3389/ti.2025.14157","DOIUrl":"10.3389/ti.2025.14157","url":null,"abstract":"This study aims to provide objective evidence for the subjectively observed increase in non-utilized donors and to investigate whether they share common risk factors, hypothesizing that the aging of the donor population may be a possible explanation. All referred deceased donors in the Netherlands between 2018 and 2023 were analyzed. A utilized donor was defined as a referred donor that resulted in at least one transplanted organ. A non-utilized donor was defined as a donor from whom no organ was transplanted as a result of the cessation. In total, 2,235 donors were defined as referred; 1,618 donors were utilized and 617 were non-utilized. A significant increase in referred donors aged >66 years was observed, together with an increase of 51% in non-utilized donors. The most frequent reasons for not utilizing a donor were found to be an agonal phase > 2 hours in DCD donors (45%) and an unacceptable medical history at screening (22%). Multivariable logistic regression analysis showed that increasing donor age (age 66-75 years OR 1.81, 95% CI 1.09-3.00), DCD donors (OR 4.37 95% CI 3.24-5.89, p < 0.01), history of hypertension (OR 1.29 95% CI 1.01-1.66, p = 0.04) and/or diabetes (OR 2.48 95% CI 1.75-3.51, p < 0.01) were associated with non-utilization. Non-utilized donors are significantly older, are more often DCD donors and have more co-morbidities, confirming the hypothesis that these donors are the more marginal donors.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"14157"},"PeriodicalIF":2.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Xenotransplantation: Evaluation of αGal-KO Porcine Livers and Lungs Using Normothermic Machine Perfusion in a Collaborative Perfusion Hub. 异种器官移植的进展：协同灌注中心用恒温机器灌注评价αGal-KO猪肝脏和肺。

IF 2.7 3区医学

Transplant International Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI: 10.3389/ti.2025.13781

S Stoerzer, S Kruszona, P Wand, H Linge, H Zlatev, K Hoeffler, J Singh, N Roters, V Muth, S Tavil, A Saipbaev, K Cvitkovic, W A Kues, P Zardo, F Ius, J Mengwasser, K Splith, K M Schmidt-Ott, T Goecke, R Schwinzer, H Niemann, A Ruhparwar, M Schmelzle, R Ramm, P Felgendreff

{"title":"Advances in Xenotransplantation: Evaluation of αGal-KO Porcine Livers and Lungs Using Normothermic Machine Perfusion in a Collaborative Perfusion Hub.","authors":"S Stoerzer, S Kruszona, P Wand, H Linge, H Zlatev, K Hoeffler, J Singh, N Roters, V Muth, S Tavil, A Saipbaev, K Cvitkovic, W A Kues, P Zardo, F Ius, J Mengwasser, K Splith, K M Schmidt-Ott, T Goecke, R Schwinzer, H Niemann, A Ruhparwar, M Schmelzle, R Ramm, P Felgendreff","doi":"10.3389/ti.2025.13781","DOIUrl":"10.3389/ti.2025.13781","url":null,"abstract":"Recently, initial clinical experience has been gained with the xenotransplantation of pig organs such as heart and kidney into terminally ill human patients in an effort to overcoming organ shortage. Here, we investigated the use of normothermic machine perfusion (NMP) to advance xenotransplantation research and develop bridging therapies for acute organ failure such as the use of pig livers as a liver dialysis system. We simultaneously analyzed livers and lungs from genetically modified pigs, carrying a knock-out of the GGTA1 gene, which is essential for xenoreactive αGal-KO-epitopes, by applying clinically established normothermic perfusion systems, solutions and human blood. Experiments involved perfusing organs with cell-free solutions as well as human erythrocyte concentrates for up to six hours, analyzing organ quality using invasive and non-invasive methods, and the isolation and analysis of immune cells from the perfusate. The results obtained show stable flow characteristics with physiological perfusion and oxygenation levels of the organs, and a largely intact organ architecture, confirmed by histological sections before and after perfusion. Overall, this study demonstrates the feasibility of normothermic machine perfusion of xenogeneic organs by an interdisciplinary team, thus paving the way for clinical applications of porcine xenografts involving NMP.","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"38 ","pages":"13781"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0