Heart transplantation: challenges facing the field.
Heart transplantation: challenges facing the field.
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DOI：
10.1101/cshperspect.a015636
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Madsen JC
中科院分区：
文献类型：
--
作者：
Tonsho M;Michel S;Ahmed Z;Alessandrini A;Madsen JC
在过去的45年里，心脏移植领域取得了重大进展。心脏移植后的1年存活率从20世纪70年代的30%提高到21世纪初的近90%。然而，长期结果几乎没有变化。这主要是由于慢性排斥、恶性肿瘤和慢性免疫抑制的有害副作用。此外，在过去的十年中，出现了新的挑战，如日益复杂的受体和抗体介导的排斥反应。大多数（如果不是全部的话）长期存活的这些障碍可以通过诱导移植耐受来预防或改善，其中受体的免疫系统被说服不产生针对供体抗原的破坏性免疫应答，从而消除对慢性免疫抑制的需要。然而，与肾脏等其他同种异体移植物不同，心脏似乎是耐受性器官。了解为什么像肾脏和肝脏这样的器官容易诱导耐受，而其他器官如心脏和肺则具有耐受性，可以帮助我们实现人类心脏移植受者的长期无免疫抑制生存。它还可以推进猪到人的异种移植领域，如果成功，将消除器官短缺问题。当然，心脏移植领域还有其他的未来，可能包括全机械支持，干细胞或生物工程全器官的应用。哪种模式将首先达到实现无限、长期、循环支持的最终目标，同时对寿命或生活方式的风险最小，目前尚不清楚，但在这些领域都取得了重大进展。
There has been significant progress in the field of heart transplantation over the last 45 years. The 1-yr survival rates following heart transplantation have improved from 30% in the 1970s to almost 90% in the 2000s. However, there has been little change in long-term outcomes. This is mainly due to chronic rejection, malignancy, and the detrimental side effects of chronic immunosuppression. In addition, over the last decade, new challenges have arisen such as increasingly complicated recipients and antibody-mediated rejection. Most, if not all, of these obstacles to long-term survival could be prevented or ameliorated by the induction of transplant tolerance wherein the recipient’s immune system is persuaded not to mount a damaging immune response against donor antigens, thus eliminating the need for chronic immunosuppression. However, the heart, as opposed to other allografts like kidneys, appears to be a tolerance-resistant organ. Understanding why organs like kidneys and livers are prone to tolerance induction, whereas others like hearts and lungs are tolerance-resistant, could aid in our attempts to achieve long-term, immunosuppression-free survival in human heart transplant recipients. It could also advance the field of pig-to-human xenotransplantation, which, if successful, would eliminate the organ shortage problem. Of course, there are alternative futures to the field of heart transplantation that may include the application of total mechanical support, stem cells, or bioengineered whole organs. Which modality will be the first to reach the ultimate goal of achieving unlimited, long-term, circulatory support with minimal risk to longevity or lifestyle is unknown, but significant progress in being made in each of these areas.
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