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猪肝脏研发及临床转化中的经验教训——通过常温机器灌注战胜器官时钟

Lessons Learned in Research and Development With Porcine Livers and the Clinical Translation-Beating the Organ Clock With Normothermic Machine Perfusion.

作者信息

Schuler Martin Jörg, Becker Dustin, Machacek David, Kalt Fabian, Fröhlich Rafael, Lopez-Lopez Victor, Onder Christopher, Oberholzer Jose, Eshmuminov Dilmurodjon

机构信息

ASSCO Engineering AG, Dietikon, Switzerland.

Institute for Dynamic Systems and Control, ETH Zurich D-MAVT, Zurich, Switzerland.

出版信息

Clin Transplant. 2025 Aug;39(8):e70264. doi: 10.1111/ctr.70264.

Abstract

Short-term (less than 24 h) normothermic liver perfusion devices are currently used in clinical practice. They improve logistics, simplify recipient matching, and aid in transplant decisions. At the same time, researchers globally are actively working on technologies to extend organ preservation times, mainly for transplantation. This paper investigates what it takes to keep a liver viable ex vivo using machine perfusion, outlining the essential conditions and key viability criteria during perfusion. The project's aim was to create a long-term liver perfusion machine that mimics the body's core functions, offering an artificial environment as close as possible to natural in vivo physiological conditions. After a successful 5-year development phase with porcine livers, the technology was then tested on two prototypes using human livers that were unsuitable for transplantation. This paper shares the experience, discoveries, and lessons learned during the research and development of a long-term liver perfusion machine. It considers both the current state of the art and existing clinical practices in transplantation. The viability criteria are also discussed from the perspective of long-term perfusion, especially since there's no current consensus in this area. Furthermore, the potential applications of these technologies are described. Overall, this long-term perfusion technology is seen as a platform that could unlock exciting new clinical applications, offering significant patient benefits that may outweigh the economic challenges. Nevertheless, considerable research is still needed to bring these concepts and ideas into routine clinical practice.

摘要

短期(少于24小时)常温肝脏灌注装置目前已应用于临床实践。它们改善了后勤保障,简化了受体匹配,并有助于做出移植决策。与此同时,全球的研究人员都在积极致力于延长器官保存时间的技术,主要用于移植。本文研究了使用机器灌注使肝脏在体外保持存活所需的条件,概述了灌注过程中的基本条件和关键存活标准。该项目的目标是制造一台能模拟人体核心功能的长期肝脏灌注机器,提供一个尽可能接近自然体内生理条件的人工环境。在使用猪肝成功进行了5年的开发阶段后,该技术随后在两台使用不适合移植的人类肝脏的原型机上进行了测试。本文分享了在长期肝脏灌注机器研发过程中的经验、发现和教训。它考虑了当前的技术水平和移植领域现有的临床实践。还从长期灌注的角度讨论了存活标准,特别是因为该领域目前尚无共识。此外,还描述了这些技术的潜在应用。总体而言,这种长期灌注技术被视为一个可以开启令人兴奋的新临床应用的平台,为患者带来显著益处,可能超过经济挑战。然而,仍需要进行大量研究才能将这些概念和想法引入常规临床实践。

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