Xenotransplantation: The next quarter century

Q4 Medicine
A. Joseph Tector , Matt Tector , Rodrigo Vianna , Andrew Adams
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引用次数: 0

Abstract

Transplantation has become a preferred therapy for the treatment of end stage organ failure, improving the quality and duration of recipients lives. The major limitation of organ transplantation is the shortage of suitable donor organs available for clinical use. Xenotransplantation using genetically modified pig organs could provide an unlimited source of organs, allowing all patients in need to receive a transplant in a timely fashion. Xenotransplantation was limited to the experimental realm because of the presence of anti-pig antibodies that are present in the blood of every human (1, 2).
The development of genetic engineering tools, especially CRISPR/Cas9 and somatic cell nuclear transfer made it possible to create pigs missing key glycan pig antigens so that the antibodies did not bind to the new pig (3-5). Preclinical results using kidneys from new donor pigs has improved to the point where nonhuman primate recipients are living for more than 4 years (Andrew Adams personal communication). The improvements in survival seen in preclinical models has led to clinical attempts at heart and kidney xenotransplantation (6, 7). Thus far in the first 5 clinical xenotransplant cases success has been modest, with only one graft (kidney) functioning past 60 days to date. The other patients receiving pig xenografts (2 hearts and 2 kidneys) succumbed to early antibody mediated rejection (AMR) (7-9). Nevertheless, the developments in preclinical and compassionate use xenotransplantation have resulted in the first FDA approved clinical trial with renal xenotransplantation. This article will deal with the issues that are likely to be the focus of the next 25 years with regards to development of clinical xenotransplantation.
异种移植:下一个四分之一个世纪
移植已成为治疗终末期器官衰竭的首选治疗方法,提高了受者的生活质量和寿命。器官移植的主要限制是缺乏适合临床使用的供体器官。使用转基因猪器官的异种移植可以提供无限的器官来源,使所有需要移植的患者都能及时接受移植。异种移植被限制在实验领域,因为每个人的血液中都存在抗猪抗体(1,2)。基因工程工具的发展,特别是CRISPR/Cas9和体细胞核移植,使得制造出缺少关键糖聚糖猪抗原的猪成为可能,这样抗体就不会与新猪结合(3-5)。使用新供体猪的肾脏的临床前结果已经得到改善,非人类灵长类动物受体的寿命超过4年(Andrew Adams个人通信)。在临床前模型中观察到的生存率的提高导致了心脏和肾脏异种移植的临床尝试(6,7)。到目前为止,在前5例临床异种移植病例中,成功的情况并不多,迄今为止只有一例移植(肾脏)功能超过60天。其他接受猪异种移植(2个心脏和2个肾脏)的患者出现早期抗体介导的排斥反应(AMR)(7-9)。尽管如此,临床前和同情使用异种移植的发展导致了第一个FDA批准的肾脏异种移植临床试验。这篇文章将处理的问题,可能是未来25年的重点,关于临床异种移植的发展。
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
Transplantation Reports
Transplantation Reports Medicine-Transplantation
CiteScore
0.60
自引率
0.00%
发文量
24
审稿时长
101 days
期刊介绍: To provide to national and regional audiences experiences unique to them or confirming of broader concepts originating in large controlled trials. All aspects of organ, tissue and cell transplantation clinically and experimentally. Transplantation Reports will provide in-depth representation of emerging preclinical, impactful and clinical experiences. -Original basic or clinical science articles that represent initial limited experiences as preliminary reports. -Clinical trials of therapies previously well documented in large trials but now tested in limited, special, ethnic or clinically unique patient populations. -Case studies that confirm prior reports but have occurred in patients displaying unique clinical characteristics such as ethnicities or rarely associated co-morbidities. Transplantation Reports offers these benefits: -Fast and fair peer review -Rapid, article-based publication -Unrivalled visibility and exposure for your research -Immediate, free and permanent access to your paper on Science Direct -Immediately citable using the article DOI
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