Xenotransplantation: future frontiers and challenges.

IF 1.8 4区 医学 Q3 TRANSPLANTATION
Ian S Jaffe, Imad Aljabban, Jeffrey M Stern
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引用次数: 0

Abstract

Purpose of review: Recent advancements in genetic engineering have propelled the field of xenotransplantation from preclinical models to early compassionate use cases. As first-in-human clinical trials (FIHCTs) approach, we examine recent developments, ethical and regulatory challenges, immunological considerations, and the clinical infrastructure necessary for successful xenotransplantation trials.

Recent findings: Expanded access transplants of pig hearts, kidneys, and livers have identified key challenges. Heart xenotransplants revealed risks of antibody-mediated rejection and zoonotic infections, while kidney xenotransplants suggest that patient selection, rather than immune rejection, may have caused failures. While there has been a report of auxiliary liver transplantation conducted abroad, profound thrombocytopenia poses an obstacle. As FIHCTs draw near, critical clinical challenges include determining the optimal donor genetic constructs and immunosuppressive regimens. Enrollment criteria and patient selection pose additional complexity, alongside ethical concerns such as lifelong zoonosis monitoring. Only a limited number of centers have the expertise needed to conduct these complex trials.

Summary: Xenotransplantation holds great promise as a solution to organ shortages, but success in FIHCTs will require careful design, multidisciplinary collaboration, and strong infrastructure. Addressing immunologic, ethical, and patient selection challenges will be critical. With proper preparation, xenotransplantation could transform organ transplantation.

异种移植:未来的前沿和挑战。
综述目的:基因工程的最新进展推动了异种移植领域从临床前模型发展到早期临床应用。作为首次人体临床试验(fihct)的方法,我们研究了最近的发展、伦理和监管挑战、免疫学考虑以及成功的异种移植试验所需的临床基础设施。最近的发现:扩大猪心脏、肾脏和肝脏移植的准入范围已经确定了关键的挑战。心脏异种移植显示出抗体介导的排斥反应和人畜共患感染的风险,而肾脏异种移植表明,患者选择,而不是免疫排斥,可能导致失败。虽然国外有辅助肝移植的报道,但严重的血小板减少症是一个障碍。随着fihct的临近,关键的临床挑战包括确定最佳供体遗传结构和免疫抑制方案。入组标准和患者选择带来了额外的复杂性,以及诸如终身人畜共患病监测等伦理问题。只有少数中心拥有进行这些复杂试验所需的专业知识。摘要:异种移植有望解决器官短缺问题,但fihct的成功需要精心设计、多学科合作和强大的基础设施。解决免疫、伦理和患者选择方面的挑战将是至关重要的。通过适当的准备,异种移植可以转化为器官移植。
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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