Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Department of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Front Immunol. 2020 May 12;11:631. doi: 10.3389/fimmu.2020.00631. eCollection 2020.
Organ transplantation is undergoing profound changes. Contraindications for donation have been revised in order to better meet the organ demand. The use of lower-quality organs and organs with greater preoperative damage, including those from donation after cardiac death (DCD), has become an established routine but increases the risk of graft malfunction. This risk is further aggravated by ischemia and reperfusion injury (IRI) in the process of transplantation. These circumstances demand a preservation technology that ameliorates IRI and allows for assessment of viability and function prior to transplantation. Oxygenated hypothermic and normothermic machine perfusion (MP) have emerged as valid novel modalities for advanced organ preservation and conditioning. prolonged lung preservation has resulted in successful transplantation of high-risk donor lungs. Normothermic MP of hearts and livers has displayed safe (heart) and superior (liver) preservation in randomized controlled trials (RCT). Normothermic kidney preservation for 24 h was recently established. Early clinical outcomes beyond the market entry trials indicate bioenergetics reconditioning, improved preservation of structures subject to IRI, and significant prolongation of the preservation time. The monitoring of perfusion parameters, the biochemical investigation of preservation fluids, and the assessment of tissue viability and bioenergetics function now offer a comprehensive assessment of organ quality and function . Gene and protein expression profiling, investigation of passenger leukocytes, and advanced imaging may further enhance the understanding of the condition of an organ during MP. In addition, MP offers a platform for organ reconditioning and regeneration and hence catalyzes the clinical realization of tissue engineering. Organ modification may include immunological modification and the generation of chimeric organs. While these ideas are not conceptually new, MP now offers a platform for clinical realization. Defatting of steatotic livers, modulation of inflammation during preservation in lungs, vasodilatation of livers, and hepatitis C elimination have been successfully demonstrated in experimental and clinical trials. Targeted treatment of lesions and surgical treatment or graft modification have been attempted. In this review, we address the current state of MP and advanced organ monitoring and speculate about logical future steps and how this evolution of a novel technology can result in a medial revolution.
器官移植正在发生深刻的变化。为了更好地满足器官需求，捐赠的禁忌症已经修订。使用质量较低的器官和术前损伤较大的器官，包括来自心死亡后捐赠（DCD）的器官，已成为常规做法，但会增加移植物功能障碍的风险。在移植过程中，缺血再灌注损伤（IRI）进一步加剧了这种风险。在这些情况下，需要一种保存技术来改善 IRI，并在移植前评估供体的活力和功能。充氧低温和常温机器灌注（MP）已成为先进器官保存和调理的有效新方法。长时间的肺保存导致高危供肺的成功移植。心脏和肝脏的常温 MP 在随机对照试验（RCT）中显示出安全（心脏）和优越（肝脏）的保存。常温肾脏保存 24 小时最近已经建立。市场准入试验之外的早期临床结果表明生物能量再调理、IRI 相关结构保存的改善以及保存时间的显著延长。灌注参数的监测、保存液的生化研究以及组织活力和生物能量功能的评估现在提供了对器官质量和功能的全面评估。基因和蛋白质表达谱分析、过客白细胞的研究以及高级成像可以进一步增强对 MP 期间器官状况的了解。此外，MP 为器官再调理和再生提供了平台，从而促进了组织工程的临床实现。器官修饰可能包括免疫修饰和嵌合器官的产生。虽然这些想法在概念上并不新颖，但 MP 现在为临床实现提供了平台。实验和临床试验已经成功地证明了脂肪肝的去脂、保存期间肺炎症的调节、肝脏的血管舒张以及丙型肝炎的消除。已经尝试了针对病变的靶向治疗以及手术治疗或移植物修饰。在这篇综述中，我们讨论了 MP 和先进器官监测的现状，并推测了合乎逻辑的未来步骤，以及这项新技术的发展如何导致医学革命。
