Supercooling extends preservation time of human livers
Supercooling extends preservation time of human livers
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DOI：
10.1038/s41587-019-0223-y
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发表时间：
2019-10-01
影响因子：
46.9
通讯作者：
Uygun, Korkut
中科院分区：
文献类型：
--
作者：
de Vries, Reinier J.;Tessier, Shannon N.;Uygun, Korkut
血管器官无法保存数小时以上，导致器官移植稀缺（1,2）。标准的+4℃低温保存（参考文献（1,3））将肝脏保存时间限制在12小时以内。我们的研究小组之前表明，在-6℃下的过冷无冰储存可以延长大鼠肝脏的有效保存时间（4,5）。然而，由于体积依赖的随机冰形成，将过冷保存扩展到人体器官本质上是有限的。在这里，我们描述了一种改进的过冷方案，通过减少有利的冰核位置和在机器灌注过程中使用保护剂的均匀预处理来避免人类肝脏的冷冻。我们的研究表明，人类肝脏可以在-4℃下进行过冷保存，然后进行亚恒温机器灌注，有效地延长器官的离体寿命27小时。我们的研究表明，过冷前后肝脏的活力没有变化，过冷后肝脏可以承受体外恒温再灌注血液模拟移植的压力。
The inability to preserve vascular organs beyond several hours contributes to the scarcity of organs for transplantation(1,2). Standard hypothermic preservation at +4 degrees C (refs.(1,3)) limits liver preservation to less than 12 h. Our group previously showed that supercooled ice-free storage at -6 degrees C can extend viable preservation of rat livers(4,5) However, scaling supercooling preservation to human organs is intrinsically limited because of volume-dependent stochastic ice formation. Here, we describe an improved supercooling protocol that averts freezing of human livers by minimizing favorable sites of ice nucleation and homogeneous preconditioning with protective agents during machine perfusion. We show that human livers can be stored at -4 degrees C with supercooling followed by subnormothermic machine perfusion, effectively extending the ex vivo life of the organ by 27 h. We show that viability of livers before and after supercooling is unchanged, and that after supercooling livers can withstand the stress of simulated transplantation by ex vivo normothermic reperfusion with blood.