Cardiac xenotransplantation: from concept to clinic.
Cardiac xenotransplantation: from concept to clinic.
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DOI：
10.1093/cvr/cvac180
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发表时间：
2023-02-03
影响因子：
10.8
通讯作者：
中科院分区：
文献类型：
--
作者：
对于许多晚期/晚期心力衰竭患者来说，心脏移植是最有效、最持久的治疗选择，并为高质量生活提供了最佳前景。可能挽救生命的捐赠人体器官的数量远远少于可以从新心脏中受益的人口，导致等待更换衰竭心脏的患者数量不断增加，等待名单上的死亡率很高，并且许多被认为是最佳候选者但在等待过程中病情恶化的人经常依赖临时机械支持。目前，支持左心室或双心室心脏功能的机械辅助装置是临床使用的心脏移植的唯一替代方案。不幸的是，尽管设备设计以及患者选择和管理方面取得了进步，但机械辅助的并发症发生率仍然很高，即使具有良好的结果，患者的生活质量也仅得到适度改善。转基因猪的心脏异种移植是一种新兴的新选择，狒狒异位（非生命支持）腹部和原位猪心脏移植的长期成功证明了这一点，最近“同情使用”将经过 10 种基因改造的转基因猪的心脏移植到存活了 2 个月的绝症患者体内。在这篇综述中，我们将猪心脏异种移植作为一个概念进行讨论，包括与免疫排斥、凝血失调和有害的心脏过度生长相关的病理生物学方面，以及猪预防或尽量减少这些问题的转基因策略。讨论的其他主题包括猪狒狒模型中异位和原位心脏移植实验的相关结果、微生物学和病毒学安全概念以及启动正式临床试验的功效要求。适当的监管和伦理框架以及严格的患者选择标准对于心脏异种移植的安全临床开发至关重要，我们预计将在未来几年内进行临床测试。
For many patients with terminal/advanced cardiac failure, heart transplantation is the most effective, durable treatment option, and offers the best prospects for a high quality of life. The number of potentially life-saving donated human organs is far fewer than the population who could benefit from a new heart, resulting in increasing numbers of patients awaiting replacement of their failing heart, high waitlist mortality, and frequent reliance on interim mechanical support for many of those deemed among the best candidates but who are deteriorating as they wait. Currently, mechanical assist devices supporting left ventricular or biventricular heart function are the only alternative to heart transplant that is in clinical use. Unfortunately, the complication rate with mechanical assistance remains high despite advances in device design and patient selection and management, and the quality of life of the patients even with good outcomes is only moderately improved. Cardiac xenotransplantation from genetically multi-modified (GM) organ-source pigs is an emerging new option as demonstrated by the consistent long-term success of heterotopic (non-life-supporting) abdominal and life-supporting orthotopic porcine heart transplantation in baboons, and by a recent ‘compassionate use’ transplant of the heart from a GM pig with 10 modifications into a terminally ill patient who survived for 2 months. In this review, we discuss pig heart xenotransplantation as a concept, including pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental overgrowth of the heart, as well as GM strategies in pigs to prevent or minimize these problems. Additional topics discussed include relevant results of heterotopic and orthotopic heart transplantation experiments in the pig-to-baboon model, microbiological and virologic safety concepts, and efficacy requirements for initiating formal clinical trials. An adequate regulatory and ethical framework as well as stringent criteria for the selection of patients will be critical for the safe clinical development of cardiac xenotransplantation, which we expect will be clinically tested during the next few years.
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影响因子：
3.9
作者：
Abicht, Jan-Michael;Mayr, Tanja;Brenner, Paolo
通讯作者：
Brenner, Paolo
影响因子：
3.9
作者：
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通讯作者：
Pierson, Richard N., III
影响因子：
8.9
作者：
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通讯作者：
Kirklin, James K.
影响因子：
3.9
作者：
Buermann, Anna;Petkov, Stoyan;Schwinzer, Reinhard
通讯作者：
Schwinzer, Reinhard
影响因子：
8.8
作者：
Ahrens, H. E.;Petersen, B.;Niemann, H.
通讯作者：
Niemann, H.