Buchwald Julianna E, Xu Jing, Bozorgzadeh Adel, Martins Paulo N
Division of Transplantation, Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, United States.
World J Transplant. 2020 Jan 18;10(1):1-14. doi: 10.5500/wjt.v10.i1.1.
Although the use of extended criteria donors has increased the pool of available livers for transplant, it has also introduced the need to develop improved methods of protection against ischemia-reperfusion injury (IRI), as these "marginal" organs are particularly vulnerable to IRI during the process of procurement, preservation, surgery, and post-transplantation. In this review, we explore the current basic science research investigating therapeutics administered during liver machine perfusion aimed at mitigating the effects of IRI in the liver transplantation process. These various categories of therapeutics are utilized during the perfusion process and include invoking the RNA interference pathway, utilizing defatting cocktails, and administering classes of agents such as vasodilators, anti-inflammatory drugs, human liver stem cell-derived extracellular vesicles, and δ-opioid agonists in order to reduce the damage of IRI. machine perfusion is an attractive alternative to static cold storage due to its ability to continuously perfuse the organ, effectively deliver substrates and oxygen required for cellular metabolism, therapeutically administer pharmacological or cytoprotective agents, and continuously monitor organ viability during perfusion. The use of administered therapeutics during machine liver perfusion has demonstrated promising results in basic science studies. While novel therapeutic approaches to combat IRI are being developed through basic science research, their use in clinical medicine and treatment in patients for liver transplantation has yet to be explored.
尽管使用扩大标准供体增加了可用于移植的肝脏数量，但这也带来了开发改进的预防缺血再灌注损伤（IRI）方法的需求，因为这些“边缘”器官在获取、保存、手术及移植后过程中对IRI尤为敏感。在本综述中，我们探讨了当前基础科学研究，该研究调查了在肝脏机器灌注期间给予的旨在减轻肝脏移植过程中IRI影响的治疗方法。这些各类治疗方法在灌注过程中使用，包括激活RNA干扰途径、使用去脂混合物以及给予血管扩张剂、抗炎药物、人肝干细胞衍生的细胞外囊泡和δ-阿片受体激动剂等药物类别，以减少IRI的损伤。机器灌注是静态冷藏的一种有吸引力的替代方法，因为它能够持续灌注器官，有效输送细胞代谢所需的底物和氧气，治疗性地给予药理或细胞保护剂，并在灌注期间持续监测器官活力。在肝脏机器灌注期间使用给予的治疗方法在基础科学研究中已显示出有前景的结果。虽然通过基础科学研究正在开发对抗IRI的新治疗方法，但它们在临床医学中的应用以及在肝移植患者中的治疗尚未得到探索。
