Future directions for xenotransplantation in lungs.

IF 1.8 4区 医学 Q3 TRANSPLANTATION
Hidetaka Hara, Hisashi Sahara, Toyofumi Fengshi Chen-Yoshikawa
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引用次数: 0

Abstract

Purpose of review: Advancements in preclinical xenotransplant studies have opened doors for clinical heart and kidney xenotransplantation. This review assesses recent progress in lung xenotransplantation research and its potential clinical implications.

Recent findings: The efficacy of the humanized von Willebrand factor in reducing platelet sequestration in ex-vivo and in-vivo lung xenotransplant models was showcased. Combining human tissue factor pathway inhibitor and CD47 expression with selectin and integrin inhibition delayed neutrophil and platelet sequestration. Enhanced expression of human complement regulatory proteins and thrombomodulin in genetically engineered pig lungs improved graft survival by reducing platelet activation and modulating coagulation disruptions. Knocking out the CMAH gene decreased antibody-mediated inflammation and coagulation activation, enhancing compatibility for human transplantation. Furthermore, CMAH gene knockout in pigs attenuated sialoadhesin-dependent binding of human erythrocytes to porcine macrophages, mitigating erythrocyte sequestration and anemia. Meanwhile, in-vivo experiments demonstrated extended survival of xenografts for up to 31 days with multiple genetic modifications and comprehensive treatment strategies.

Summary: Experiments have uncovered vital insights for successful xenotransplantation, driving further research into immunosuppressive therapy and genetically modified pigs. This will ultimately pave the way for clinical trials designed to improve outcomes for patients with end-stage lung disease.

肺部异种移植的未来方向。
综述目的:临床前异种移植研究的进展为临床心脏和肾脏异种移植打开了大门。本综述评估了肺异种移植研究的最新进展及其潜在的临床意义:展示了人源化von Willebrand因子在体内外肺异种移植模型中减少血小板螯合的功效。将人组织因子通路抑制剂和 CD47 表达与选择素和整合素抑制相结合,可延缓中性粒细胞和血小板螯合。在基因工程猪肺中增强人类补体调节蛋白和血栓调节蛋白的表达,通过减少血小板活化和调节凝血紊乱提高移植物存活率。敲除 CMAH 基因可减少抗体介导的炎症和凝血活化,提高人体移植的兼容性。此外,在猪体内敲除 CMAH 基因可减轻人红细胞与猪巨噬细胞的依赖性结合,从而减轻红细胞螯合和贫血。同时,体内实验表明,通过多种基因修饰和综合治疗策略,异种移植物的存活期可延长至 31 天。摘要:实验揭示了成功进行异种移植的重要见解,推动了对免疫抑制疗法和转基因猪的进一步研究。这最终将为旨在改善终末期肺病患者预后的临床试验铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
4.50%
发文量
124
审稿时长
6-12 weeks
期刊介绍: ​​​​​​Current Opinion in Organ Transplantation is an indispensable resource featuring key, up-to-date and important advances in the field from around the world. Led by renowned guest editors for each section, every bimonthly issue of Current Opinion in Organ Transplantation delivers a fresh insight into topics such as stem cell transplantation, immunosuppression, tolerance induction and organ preservation and procurement. With 18 sections in total, the journal provides a convenient and thorough review of the field and will be of interest to researchers, surgeons and other healthcare professionals alike.
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