A Standardized Approach to Orthotopic (Life-supporting) Porcine Cardiac Xenotransplantation in a Nonhuman Primate Model.
A Standardized Approach to Orthotopic (Life-supporting) Porcine Cardiac Xenotransplantation in a Nonhuman Primate Model.
复制标题
非人灵长类动物模型中原位（维持生命）猪心脏异种移植的标准化方法。
DOI：
10.1097/tp.0000000000004508
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发表时间：
2023
期刊：
影响因子：
6.2
通讯作者：
Mohiuddin,MuhammadM
中科院分区：
文献类型：
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作者：
Goerlich,CorbinE;Griffith,BartleyP;Shah,Aakash;Treffalls,JohnA;Zhang,Tianshu;Lewis,Billeta;Tatarov,Ivan;Hershfeld,Alena;Sentz,Faith;Braileanu,Gheorghe;Ayares,David;Singh,AvneeshK;Mohiuddin,MuhammadM
猪的异种心脏移植已被提议用于为需要移植的心力衰竭患者“弥合差距”。最近的临床前成功使用转基因猪供体狒狒受体已证明生存期超过6个月，与异种移植免疫生物学的现代理解和心脏异种移植的大型动物模型的持续经验。作为这一专业知识的直接结果，美国食品和药物管理局批准了第一个通过扩大单一患者的使用申请进行的基因工程心脏异种移植的人体内移植。该临床病例证明了异种移植的可行性。尽管这项人体研究证明了心脏异种移植的原理性应用，但在批准更正式的临床试验之前，可能需要食品和药物管理局对异种移植的大型动物模型的临床前试验进行进一步的监管监督。在这里，我们详细介绍了我们的手术方法，以猪灵长类动物的大动物模型的原位心脏异种移植，和灵长类动物受体的术后护理，无论是在术后的第一阶段，并在随后的几个月。我们还详细介绍了异种移植物的监测方法和常见的问题，出现在术后期间具体到这个模型和方法来克服它们。这些研究需要多学科团队和原位移植（心脏手术，麻醉和心肺转流术），免疫学，基因工程和处理大型动物供体和受体的经验，这些都在这里描述。这篇文章旨在减少进入一个热情不断增长的领域的障碍，但需要专业知识和经验才能取得成功。
Cardiac xenotransplantation from swine has been proposed to “bridge the gap” in supply for heart failure patients requiring transplantation. Recent preclinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 mo, with a modern understanding of xenotransplantation immunobiology and continued experience with large animal models of cardiac xenotransplantation. As a direct result of this expertise, the Food and Drug Administration approved the first in-human transplantation of a genetically engineered cardiac xenograft through an expanded access application for a single patient. This clinical case demonstrated the feasibility of xenotransplantation. Although this human study demonstrated proof-of-principle application of cardiac xenotransplantation, further regulatory oversight by the Food and Drug Administration may be required with preclinical trials in large animal models of xenotransplantation with long-term survival before approval of a more formalized clinical trial. Here we detail our surgical approach to pig-to-primate large animal models of orthotopic cardiac xenotransplantation, and the postoperative care of the primate recipient, both in the immediate postoperative period and in the months thereafter. We also detail xenograft surveillance methods and common issues that arise in the postoperative period specific to this model and ways to overcome them. These studies require multidisciplinary teams and expertise in orthotopic transplantation (cardiac surgery, anesthesia, and cardiopulmonary bypass), immunology, genetic engineering, and experience in handling large animal donors and recipients, which are described here. This article serves to reduce the barriers to entry into a field with ever-growing enthusiasm, but demands expertise knowledge and experience to be successful.