An integrated perfusion machine preserves injured human livers for 1 week
An integrated perfusion machine preserves injured human livers for 1 week
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DOI：
10.1038/s41587-019-0374-x
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发表时间：
2020-01-13
影响因子：
46.9
通讯作者：
Clavien, Pierre-Alain
中科院分区：
文献类型：
--
作者：
Eshmuminov, Dilmurodjon;Becker, Dustin;Clavien, Pierre-Alain
肝脏在复杂的灌注系统中长期保存。如果能够将代谢活跃的肝脏离体保存 1 周或更长时间，则可以修复质量较差的肝脏，否则这些肝脏将无法进行移植。目前的常温灌注方法只能保存人类肝脏 24 小时。在这里，我们报告了一种集成了多种核心生理功能的肝脏灌注机，包括葡萄糖水平和氧合的自动管理、废物清除和血细胞比容控制。我们使用猪肝逐步开发了该机器。多个离体参数和体内早期再灌注的研究证明了猪肝灌注 1 周的活力，无需额外的血液制品或灌注液交换。我们在十个受伤的人类肝脏上测试了这种方法，这些肝脏已被所有欧洲中心拒绝移植。经过 7 天的灌注后，六个人类肝脏显示出胆汁生成、凝血因子合成、维持细胞能量 (ATP) 和完整肝脏结构等功能的保留。
Livers are stored long term in a sophisticated perfusion system.The ability to preserve metabolically active livers ex vivo for 1 week or more could allow repair of poor-quality livers that would otherwise be declined for transplantation. Current approaches for normothermic perfusion can preserve human livers for only 24 h. Here we report a liver perfusion machine that integrates multiple core physiological functions, including automated management of glucose levels and oxygenation, waste-product removal and hematocrit control. We developed the machine in a stepwise fashion using pig livers. Study of multiple ex vivo parameters and early phase reperfusion in vivo demonstrated the viability of pig livers perfused for 1 week without the need for additional blood products or perfusate exchange. We tested the approach on ten injured human livers that had been declined for transplantation by all European centers. After a 7-d perfusion, six of the human livers showed preserved function as indicated by bile production, synthesis of coagulation factors, maintained cellular energy (ATP) and intact liver structure.