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异种交叉循环用于体外人类肝脏的生理支持和恢复。

Xenogeneic cross-circulation for physiological support and recovery of ex vivo human livers.

机构信息

Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Department of Cardiac Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

出版信息

Hepatology. 2023 Sep 1;78(3):820-834. doi: 10.1097/HEP.0000000000000357. Epub 2023 Mar 30.

DOI:10.1097/HEP.0000000000000357
PMID:36988383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10440302/
Abstract

BACKGROUND AND AIMS

The scarcity of suitable donor livers highlights a continuing need for innovation to recover organs with reversible injuries in liver transplantation.

APPROACH AND RESULTS

Explanted human donor livers (n = 5) declined for transplantation were supported using xenogeneic cross-circulation of whole blood between livers and xeno-support swine. Livers and swine were assessed over 24 hours of xeno-support. Livers maintained normal global appearance, uniform perfusion, and preservation of histologic and subcellular architecture. Oxygen consumption increased by 75% ( p = 0.16). Lactate clearance increased from -0.4 ± 15.5% to 31.4 ± 19.0% ( p = 0.02). Blinded histopathologic assessment demonstrated improved injury scores at 24 hours compared with 12 hours. Vascular integrity and vasoconstrictive function were preserved. Bile volume and cholangiocellular viability markers improved for all livers. Biliary structural integrity was maintained.

CONCLUSIONS

Xenogeneic cross-circulation provided multisystem physiological regulation of ex vivo human livers that enabled functional rehabilitation, histopathologic recovery, and improvement of viability markers. We envision xenogeneic cross-circulation as a complementary technique to other organ-preservation technologies in the recovery of marginal donor livers or as a research tool in the development of advanced bioengineering and pharmacologic strategies for organ recovery and rehabilitation.

摘要

背景与目的

合适供体肝脏的短缺突出表明，在肝移植中需要不断创新以恢复具有可逆性损伤的器官。

方法与结果

对 5 例因移植而被淘汰的人供体肝脏进行异种交叉全血循环支持，即肝脏与异种支持猪之间的异种交叉全血循环。对异种支持下的肝脏和猪进行了 24 小时的评估。肝脏保持了正常的整体外观、均匀的灌注以及组织学和亚细胞结构的保存。氧耗增加了 75%（p = 0.16）。乳酸清除率从-0.4 ± 15.5%增加到 31.4 ± 19.0%（p = 0.02）。盲法组织病理学评估显示，与 12 小时相比，24 小时的损伤评分有所改善。血管完整性和血管收缩功能得以保留。所有肝脏的胆汁体积和胆管细胞活力标志物均有所改善。胆管结构完整性得以维持。

结论

异种交叉循环为离体人肝脏提供了多系统的生理调节，使肝脏能够进行功能恢复、组织病理学恢复和活力标志物改善。我们设想异种交叉循环是其他器官保存技术的补充技术，可以用于恢复边缘供体肝脏，也可以作为开发先进的生物工程和药理学策略以恢复和修复器官的研究工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/b132a1ab504d/hep-78-820-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/c1b8febf7f04/hep-78-820-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/dce290fa3ae8/hep-78-820-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/fe739c069ca2/hep-78-820-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/bd51e8308494/hep-78-820-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/ce503ed20597/hep-78-820-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/326354874a79/hep-78-820-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/b132a1ab504d/hep-78-820-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/c1b8febf7f04/hep-78-820-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/dce290fa3ae8/hep-78-820-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/fe739c069ca2/hep-78-820-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/bd51e8308494/hep-78-820-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/ce503ed20597/hep-78-820-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/326354874a79/hep-78-820-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4044/10442083/b132a1ab504d/hep-78-820-g007.jpg

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