Zhao Yajin, Main Kimberly, Aujla Tanroop, Keshavjee Shaf, Liu Mingyao
Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.
Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cells. 2023 Sep 17;12(18):2296. doi: 10.3390/cells12182296.
Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, and allograft rejection. The specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.
器官移植仍然是终末期器官功能障碍患者唯一的治疗选择。然而，存在许多限制因素挑战其临床应用，包括器官捐赠短缺、捐赠器官的质量、器官保存和再灌注期间的损伤、原发性和慢性移植物功能障碍、急性和慢性排斥反应、感染以及移植后患者的致癌作用。急性和慢性炎症以及细胞死亡是移植物损伤的两个主要潜在机制。坏死性凋亡是一种参与多种疾病的程序性细胞死亡类型，并且已经在包括肾脏、心脏、肝脏和肺在内的所有主要实体器官移植中进行了研究。它由潜在的供体器官状况（例如年龄、饮酒、脂肪肝、出血性休克、循环死亡后捐赠等）、保存条件和再灌注以及同种异体移植排斥反应决定。坏死性凋亡的具体分子机制已在器官移植环境中被揭示，并且已确定了潜在的靶向药物。我们希望这篇综述文章将促进更多的临床研究，以确定坏死性凋亡和其他类型的程序性细胞死亡在实体器官移植中的作用，从而减轻缺血再灌注损伤和移植物排斥反应的临床负担。
