Department of Surgery, Division of Transplantation, UMass Memorial Hospital, University of Massachusetts, Worcester, MA.
Transplantation. 2020 Sep;104(9):1792-1803. doi: 10.1097/TP.0000000000003295.
Because of the high demand of organs, the usage of marginal grafts has increased. These marginal organs have a higher risk of developing ischemia-reperfusion injury, which can lead to posttransplant complications. Ex situ machine perfusion (MP), compared with the traditional static cold storage, may better protect these organs from ischemia-reperfusion injury. In addition, MP can also act as a platform for dynamic administration of pharmacological agents or gene therapy to further improve transplant outcomes. Numerous therapeutic agents have been studied under both hypothermic (1-8°C) and normothermic settings. Here, we review all the therapeutics used during MP in different organ systems (lung, liver, kidney, heart). The major categories of therapeutic agents include vasodilators, mesenchymal stem cells, antiinflammatory agents, antiinfection agents, siRNA, and defatting agents. Numerous animal and clinical studies have examined MP therapeutic agents, some of which have even led to the successful reconditioning of discarded grafts. More clinical studies, especially randomized controlled trials, will need to be conducted in the future to solidify these promising results and to define the role of MP therapeutic agents in solid organ transplantation.
由于器官需求量大,边缘供体的使用有所增加。这些边缘器官发生缺血再灌注损伤的风险更高,这可能导致移植后并发症。与传统的静态冷藏相比,离体机器灌注 (MP) 可能更好地保护这些器官免受缺血再灌注损伤。此外,MP 还可以作为动态给予药理药物或基因治疗的平台,进一步改善移植结果。在低温(1-8°C)和常温条件下,已经研究了许多治疗药物。在这里,我们综述了在不同器官系统(肺、肝、肾、心)中 MP 中使用的所有治疗药物。治疗药物的主要类别包括血管扩张剂、间充质干细胞、抗炎药、抗感染药、siRNA 和脱脂剂。已经进行了许多动物和临床研究来检查 MP 治疗药物,其中一些甚至成功地对废弃移植物进行了再处理。未来需要进行更多的临床研究,特别是随机对照试验,以巩固这些有前途的结果,并确定 MP 治疗药物在实体器官移植中的作用。