Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?
Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?
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DOI：
10.1155/2017/2534653
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发表时间：
2017
影响因子：
4.1
通讯作者：
Byrne GW
中科院分区：
文献类型：
--
作者：
McGregor CGA;Byrne GW
异种心脏移植(CXTx)是解决供心长期短缺的有效方法。最近在免疫抑制方面的进展极大地提高了异位CXTx和维持生命的肾脏XTx的存活率。表达人类补体调节蛋白的供体基因修饰(B4GALNT2和CMAH突变)的进展也加快了，降低了供体猪器官的抗原性。这些进展现在可以结合起来，并在维持生命的非人类灵长类动物的原位临床前研究和免疫适当的模型中进行测试，以证实它们对临床CXTx计划的有效性和安全性。临床前研究还应允许器官排斥反应发展异种特异性分析和治疗以逆转排斥反应。未来临床CXTx的复杂性提出了一系列实质性和独特的监管挑战，必须加以解决以避免延误；然而，依赖于这些在NHP中支持生命的前瞻性临床前研究，似乎科学前进的道路已经被很好地定义，临床CXTx的时代正在到来。
Cardiac xenotransplantation (CXTx) is a promising solution to the chronic shortage of donor hearts. Recent advancements in immune suppression have greatly improved the survival of heterotopic CXTx, now extended beyond 2 years, and life-supporting kidney XTx. Advances in donor genetic modification (B4GALNT2 and CMAH mutations) with proven Gal-deficient donors expressing human complement regulatory protein(s) have also accelerated, reducing donor pig organ antigenicity. These advances can now be combined and tested in life-supporting orthotopic preclinical studies in nonhuman primates and immunologically appropriate models confirming their efficacy and safety for a clinical CXTx program. Preclinical studies should also allow for organ rejection to develop xenospecific assays and therapies to reverse rejection. The complexity of future clinical CXTx presents a substantial and unique set of regulatory challenges which must be addressed to avoid delay; however, dependent on these prospective life-supporting preclinical studies in NHPs, it appears that the scientific path forward is well defined and the era of clinical CXTx is approaching.
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影响因子：
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