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Machine perfusion of the liver and bioengineering
Journal of Hepatology ( IF 26.8 ) Pub Date : 2023-05-17 , DOI: 10.1016/j.jhep.2023.02.009
Andrea Schlegel 1 , Hynek Mergental 2 , Constantino Fondevila 3 , Robert J Porte 4 , Peter J Friend 5 , Philipp Dutkowski 6
Affiliation  

With the increasing number of accepted candidates on waiting lists worldwide, there is an urgent need to expand the number and the quality of donor livers. Dynamic preservation approaches have demonstrated various benefits, including improving liver function and graft survival, and reducing liver injury and post-transplant complications. Consequently, organ perfusion techniques are being used in clinical practice in many countries. Despite this success, a proportion of livers do not meet current viability tests required for transplantation, even with the use of modern perfusion techniques. Therefore, devices are needed to further optimise machine liver perfusion – one promising option is to prolong machine liver perfusion for several days, with ex situ treatment of perfused livers. For example, stem cells, senolytics, or molecules targeting mitochondria or downstream signalling can be administered during long-term liver perfusion to modulate repair mechanisms and regeneration. Besides, today’s perfusion equipment is also designed to enable the use of various liver bioengineering techniques, to develop scaffolds or for their re-cellularisation. Cells or entire livers can also undergo gene modulation to modify animal livers for xenotransplantation, to directly treat injured organs or to repopulate such scaffolds with “repaired” autologous cells. This review first discusses current strategies to improve the quality of donor livers, and secondly reports on bioengineering techniques to design optimised organs during machine perfusion. Current practice, as well as the benefits and challenges associated with these different perfusion strategies are discussed.



中文翻译:

肝脏机器灌注与生物工程

随着全球等候名单上接受的候选者数量不断增加,迫切需要扩大供肝的数量和质量。动态保存方法已证明具有多种益处,包括改善肝功能和移植物存活,以及减少肝损伤和移植后并发症。因此,器官灌注技术正在许多国家应用于临床实践。尽管取得了这一成功,但即使使用现代灌注技术,仍有一部分肝脏不符合当前移植所需的活力测试。因此,需要进一步优化机器肝脏灌注的设备——一种有前途的选择是通过异位将机器肝脏灌注延长几天灌注肝脏的治疗。例如,可以在长期肝脏灌注期间施用干细胞、senolytics或靶向线粒体或下游信号传导的分子,以调节修复机制和再生。此外,当今的灌注设备还旨在能够使用各种肝脏生物工程技术,开发支架或对其进行再细胞化。细胞或整个肝脏也可以进行基因调节,以修改动物肝脏以进行异种移植,直接治疗受损器官或用“修复”的自体细胞重新填充此类支架。这篇综述首先讨论了当前提高供体肝脏质量的策略,其次报告了在机器灌注过程中设计优化器官的生物工程技术。目前的实践,

更新日期:2023-05-18
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