The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome?
The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome?
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DOI：
10.1007/s00246-018-1998-1
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发表时间：
2019-02-01
影响因子：
1.6
通讯作者：
Cooper, David K. C.
中科院分区：
文献类型：
--
作者：
Cleveland, David;Banks, C. Adam;Cooper, David K. C.
新生儿心脏移植治疗左心发育不全综合征（HLHS）与老年受者相比具有良好的长期存活率。然而，由于供体心脏严重短缺，以及移植前长时间等待的相关死亡率，新生儿心脏移植受到很大限制。这导致了分期手术姑息治疗作为HLHS的一线手术治疗的发展。基因工程和异种移植的最新进展提供了复制新生儿心脏同种异体移植的优异结果的潜力，同时通过转基因猪到人的新生儿心脏异种移植消除等待名单相关的死亡率。除新生儿中的不成熟B细胞应答外，主要猪抗原的消除允许诱导B细胞耐受的潜力。此外，相对成熟的新生儿T细胞反应可以通过在手术时切除胸腺结合供体特异性猪胸腺移植来重新编程宿主的T细胞以识别异种移植物作为宿主组织来降低。鉴于最近基因工程猪到狒狒心脏异种移植的移植物存活率显着提高，我们建议现在是考虑进行研究以推进心脏异种移植作为HLHS患者治疗选择的潜在临床应用的时候了。采用异种心脏移植可以彻底改变复杂先天性心脏病的治疗方法，并在儿科心脏移植领域开辟新的篇章。
Neonatal cardiac transplantation for hypoplastic left heart syndrome (HLHS) is associated with excellent long-term survival compared to older recipients. However, heart transplantation for neonates is greatly limited by the critical shortage of donor hearts, and by the associated mortality of the long pre-transplant waiting period. This led to the development of staged surgical palliation as the first-line surgical therapy for HLHS. Recent advances in genetic engineering and xenotransplantation have provided the potential to replicate the excellent results of neonatal cardiac allotransplantation while eliminating wait-list-associated mortality through genetically modified pig-to-human neonatal cardiac xenotransplantation. The elimination of the major pig antigens in addition to the immature B-cell response in neonates allows for the potential to induce B-cell tolerance. Additionally, the relatively mature neonatal T-cell response could be reduced by thymectomy at the time of operation combined with donor-specific pig thymus transplantation to reprogram the host's T-cells to recognize the xenograft as host tissue. In light of the recent significantly increased graft survival of genetically-engineered pig-to-baboon cardiac xenotransplantation, we propose that now is the time to consider devoting research to advance the potential clinical application of cardiac xenotransplantation as a treatment option for patients with HLHS. Employing cardiac xenotransplantation could revolutionize therapy for complex congenital heart defects and open a new chapter in the field of pediatric cardiac transplantation.