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转基因猪-人异种心脏移植案例分析
作者:小柯机器人 发布时间:2022/6/26 12:33:22

美国马里兰大学医学院Bartley P. Griffith和Muhammad M. Mohiuddin团队研究了转基因猪-人心脏异种移植的效果。2022年6月22日,《新英格兰医学杂志》发表了这一成果。

一名57岁患有非缺血性心肌病、依赖静脉材料体外膜肺氧合(ECMO)、不适宜接受包括传统同种异体移植在内的标准疗法的男子,接受了一个来自10个单独基因编辑的转基因猪源动物的心脏移植。免疫抑制基于CD40阻断。患者已脱离ECMO,异种移植物功能正常,无明显排斥反应。

异种移植物在移植后第49天突然出现舒张性增厚和衰竭,生命支持在第60天停止。尸检发现异种移植体水肿,重量几乎增加了一倍。组织学检查显示散在的心肌细胞坏死、间质水肿和红细胞外渗,没有微血管血栓形成的证据,这些发现与典型的排斥反应不一致。目前正在进行研究,以确定导致这些变化的机制。

附:英文原文

Title: Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

Author: Bartley P. Griffith, M.D.,, Corbin E. Goerlich, M.D., Ph.D.,, Avneesh K. Singh, Ph.D.,, Martine Rothblatt, Ph.D.,, Christine L. Lau, M.D.,, Aakash Shah, M.D.,, Marc Lorber, M.D.,, Alison Grazioli, M.D.,, Kapil K. Saharia, M.D.,, Susie N. Hong, M.D.,, Susan M. Joseph, M.D.,, David Ayares, Ph.D.,, and Muhammad M. Mohiuddin, M.D.

Issue&Volume: 2022-06-22

Abstract:

SummaryA 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis — findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.)

DOI: 10.1056/NEJMoa2201422

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2201422

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home