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常规冷藏会导致猪到灵长类动物肾异种移植中出现超急性移植物丢失;低温机器灌注可能是异种移植中更可取的保存方式。

Routine cold storage leads to hyperacute graft loss in pig-to-primate kidney xenotransplantation; hypothermic machine perfusion may be preferred preservation modality in xenotransplantation.

作者信息

Yamada Kazuhiko, Hisadome Yu, Eisenson Daniel, Chen WeiLi, Schulick Alex, Santillan Michelle, Luo Adam, Casella Kelly, Gu Du, Sekijima Mitsuhiro, Sahara Hisashi, Warren Daniel, Cameron Andrew, Iwase Hayato, Shenderov Eugene

机构信息

The Johns Hopkins University School of Medicine.

Kagoshima University.

出版信息

Res Sq. 2024 Dec 18:rs.3.rs-5220149. doi: 10.21203/rs.3.rs-5220149/v1.

DOI:10.21203/rs.3.rs-5220149/v1
PMID:39764145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11702802/
Abstract

Xenotransplantation (XTx) is an increasingly realistic solution to the organ shortage. Clinical XTx may require off-site procurement in a designated pathogen free (DPF) facility necessitating a period of cold ischemic time during transportation. This study evaluates the impact of different kidney preservation strategies on early graft function in pig-to-baboon XTx in a series of eight cases of pig-to-baboon xenotransplantation performed after five hours of cold ischemic time and compares these results to six cases of pig-to-baboon xenotransplantation performed with minimal ischemic time. Our data indicates that porcine kidneys appear to be particularly sensitive to IRI after cold preservation, especially across xenogeneic barriers, and routine static cold storage leads to hyperacute graft loss even in recipients with low levels of preformed antibodies. Hypothermic machine perfusion minimizes IRI and may prevent early xenograft loss.

摘要

异种移植(XTx)是解决器官短缺问题日益可行的办法。临床异种移植可能需要在指定的无特定病原体(DPF)设施中进行异地采购,这就需要在运输过程中有一段冷缺血时间。本研究评估了不同肾脏保存策略对猪到狒狒异种移植早期移植物功能的影响,该研究系列包括8例冷缺血5小时后进行的猪到狒狒异种移植,并将这些结果与6例缺血时间最短的猪到狒狒异种移植病例进行比较。我们的数据表明,猪肾在冷保存后似乎对缺血再灌注损伤(IRI)特别敏感,尤其是跨越异种屏障时,常规静态冷藏即使在预存抗体水平较低的受者中也会导致超急性移植物丢失。低温机器灌注可将IRI降至最低,并可能防止早期异种移植物丢失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/bef68b410116/nihpp-rs5220149v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/79cec548d107/nihpp-rs5220149v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/2fb69d6032d2/nihpp-rs5220149v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/71a941b14fc5/nihpp-rs5220149v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/30b81f2aebcb/nihpp-rs5220149v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/fabc8e589096/nihpp-rs5220149v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/bef68b410116/nihpp-rs5220149v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/79cec548d107/nihpp-rs5220149v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/2fb69d6032d2/nihpp-rs5220149v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/71a941b14fc5/nihpp-rs5220149v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/30b81f2aebcb/nihpp-rs5220149v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/fabc8e589096/nihpp-rs5220149v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82f0/11702802/bef68b410116/nihpp-rs5220149v1-f0006.jpg

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本文引用的文献

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Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs.使用 10GE 供体猪进行连续的生命支持猪肾异种移植,结果一致的存活。
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Uromodulin biology.尿调素生物学。
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Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.缺血再灌注损伤:分子机制与治疗靶点。
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Gp78 deficiency in hepatocytes alleviates hepatic ischemia-reperfusion injury via suppressing ACSL4-mediated ferroptosis.肝细胞中 Gp78 的缺失通过抑制 ACSL4 介导的铁死亡缓解肝脏缺血再灌注损伤。
Cell Death Dis. 2023 Dec 8;14(12):810. doi: 10.1038/s41419-023-06294-x.
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Design and testing of a humanized porcine donor for xenotransplantation.用于异种移植的人性化猪供体的设计和测试。
Nature. 2023 Oct;622(7982):393-401. doi: 10.1038/s41586-023-06594-4. Epub 2023 Oct 11.
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Substantial downregulation of mitochondrial and peroxisomal proteins during acute kidney injury revealed by data-independent acquisition proteomics.数据非依赖性采集蛋白质组学揭示急性肾损伤过程中线粒体和过氧化物酶体蛋白的大量下调。
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Early Growth Response 1 Contributes to Renal IR Injury by Inducing Proximal Tubular Cell Apoptosis.早期生长反应因子 1 通过诱导近端肾小管细胞凋亡促进肾缺血再灌注损伤。
Int J Mol Sci. 2023 Sep 19;24(18):14295. doi: 10.3390/ijms241814295.
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Hypothermia or Machine Perfusion in Kidney Donors.肾脏供体中的低温保存或机器灌注
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