Establishing a Platform for 1-Wk Normothermic Machine Perfusion of Donor Livers.

IF 4.9 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2026-10-01 DOI:10.1097/TP.0000000000005915

Julia Hofmann, Christina Bogensperger, Andras T Meszaros, Madita L Buch, Florian Nardin, Benno Cardini, Bettina Zelger, Martin Hermann, Margot Fodor, Franka Messner, Fabian Scherbauer, Magdalena Bordt, Felix J Krendl, Hannah Esser, Silvia Oberparleiter, Valeria Berchtold, Marlene Pühringer, Simon Mathis, Gabriel Putzer, Andrea Griesmacher, Christian Irsara, Harald Schennach, Judith Martini, Stefan Scheidl, Christian Margreiter, Manuel Maglione, Annemarie Weissenbacher, Rupert Oberhuber, Dietmar Öfner, Jakob Troppmair, Thomas Resch, Theresa Hautz, Stefan Schneeberger

{"title":"Establishing a Platform for 1-Wk Normothermic Machine Perfusion of Donor Livers.","authors":"Julia Hofmann, Christina Bogensperger, Andras T Meszaros, Madita L Buch, Florian Nardin, Benno Cardini, Bettina Zelger, Martin Hermann, Margot Fodor, Franka Messner, Fabian Scherbauer, Magdalena Bordt, Felix J Krendl, Hannah Esser, Silvia Oberparleiter, Valeria Berchtold, Marlene Pühringer, Simon Mathis, Gabriel Putzer, Andrea Griesmacher, Christian Irsara, Harald Schennach, Judith Martini, Stefan Scheidl, Christian Margreiter, Manuel Maglione, Annemarie Weissenbacher, Rupert Oberhuber, Dietmar Öfner, Jakob Troppmair, Thomas Resch, Theresa Hautz, Stefan Schneeberger","doi":"10.1097/TP.0000000000005915","DOIUrl":null,"url":null,"abstract":"Background: Although short-term (24 h) normothermic machine perfusion (NMP) is suitable to assess liver quality before transplantation, prolonged NMP offers the potential for modification, regeneration, and repair of marginal organs. We systematically aimed for the development of a reproducible perfusion protocol for long-term ex situ liver preservation (LTP), using a commercially available perfusion device without hardware modification.Methods: Livers retrieved from domestic pigs (N = 18) were perfused for up to 7 d (OrganOx Metra). A precision-cut liver slice culture model was applied to assess and determine the perfusate recipe. The perfusion protocol was assessed and validated in a stepwise process and later evaluated in nontransplanted human livers (N = 22).Results: The stepwise development using porcine livers finally resulted in 7-d perfusion with stable function and preserved morphology. Key advancements include red blood cell substitution, bile excretion modifications, and expanded antiinfective therapy. Applying the perfusion protocol in nontransplantable human donor livers enabled 7-d NMP in 4 livers, while control livers deteriorated after 66 [48-84] h NMP. Preserved bile production, low-levels of free hemoglobin and a low-degree of inflammation were identified as key factors for successful LTP.Conclusions: Seven-day preservation of porcine and human livers using the LTP protocol in an unmodified, commercial perfusion system is feasible; thus, the model system is suitable for treating and recovering livers, which may help to limit global organ shortage.","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TP.0000000000005915","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Although short-term (24 h) normothermic machine perfusion (NMP) is suitable to assess liver quality before transplantation, prolonged NMP offers the potential for modification, regeneration, and repair of marginal organs. We systematically aimed for the development of a reproducible perfusion protocol for long-term ex situ liver preservation (LTP), using a commercially available perfusion device without hardware modification.

Methods: Livers retrieved from domestic pigs (N = 18) were perfused for up to 7 d (OrganOx Metra). A precision-cut liver slice culture model was applied to assess and determine the perfusate recipe. The perfusion protocol was assessed and validated in a stepwise process and later evaluated in nontransplanted human livers (N = 22).

Results: The stepwise development using porcine livers finally resulted in 7-d perfusion with stable function and preserved morphology. Key advancements include red blood cell substitution, bile excretion modifications, and expanded antiinfective therapy. Applying the perfusion protocol in nontransplantable human donor livers enabled 7-d NMP in 4 livers, while control livers deteriorated after 66 [48-84] h NMP. Preserved bile production, low-levels of free hemoglobin and a low-degree of inflammation were identified as key factors for successful LTP.

Conclusions: Seven-day preservation of porcine and human livers using the LTP protocol in an unmodified, commercial perfusion system is feasible; thus, the model system is suitable for treating and recovering livers, which may help to limit global organ shortage.

查看原文本刊更多论文

供肝1周常温机器灌注平台的建立

背景：虽然短期（24小时）恒温机器灌注（NMP）适合在移植前评估肝脏质量，但延长的NMP为边缘器官的修饰、再生和修复提供了潜力。我们系统地旨在开发一种可重复的灌注方案，用于长期非原位肝脏保存（LTP），使用一种市售的灌注装置，无需硬件修改。方法：取18只家猪肝脏灌注7 d （OrganOx Metra）。采用精确切肝片培养模型，对灌注配方进行评估和确定。灌注方案在逐步过程中进行评估和验证，随后在未移植的人类肝脏中进行评估（N = 22）。结果：用猪肝逐步培养，最终形成7 d灌注，功能稳定，形态保存。主要进展包括红细胞替代、胆汁排泄修饰和扩大抗感染治疗。在非移植的人供肝中应用灌注方案，4个肝脏在7天内实现了NMP，而对照肝脏在NMP 66 [48-84] h后恶化。保留的胆汁生成、低水平的游离血红蛋白和低程度的炎症被认为是LTP成功的关键因素。结论：在未经修改的商业灌注系统中使用LTP方案保存猪和人肝脏7天是可行的；因此，该模型系统适用于肝脏的治疗和恢复，可能有助于限制全球器官短缺。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.