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异种移植的当前挑战。

Current challenges in xenotransplantation.

机构信息

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua.

Transplant Immunology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health Padua University Hospital, Padua, Italy.

出版信息

Curr Opin Organ Transplant. 2024 Jun 1;29(3):205-211. doi: 10.1097/MOT.0000000000001146. Epub 2024 Apr 16.

Abstract

PURPOSE OF REVIEW

In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation.

RECENT FINDINGS

Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies.In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects.

SUMMARY

Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.

摘要

目的综述

近年来,异种移植科学取得了巨大进展,临床前和临床研究都取得了重大进展。本文旨在描述为克服可能阻碍临床异种移植转化和成功应用的潜在障碍而开发的最新知识和方法的最新尖端进展。

最近的发现

临床前研究表明,现在有可能将挽救生命的异种移植物的灵长类动物受体的存活时间延长至两年以上。这是通过利用基因工程方法实现的,这些方法允许生成经过专门设计的基因编辑猪,仔细选择供体和受体,并采用适当的免疫抑制策略。有鉴于此,已授权在两名人类受者中使用经过基因改造的猪心进行同情性使用,并且在人类死者中也实现了异种移植。尽管令人鼓舞,但初步结果表明,异种移植成功临床转化仍有几个挑战有待充分解决。这些挑战包括免疫、生理和生物安全方面。

总结

最近的进展为在人类中初步使用猪器官进行同情性使用铺平了道路,并为更广泛地应用临床异种移植奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9cb/11064916/82fdc24a1f74/cootr-29-205-g001.jpg

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