转基因猪-人异种心脏移植

2022-07-12 16:57

尸检发现异种移植物水肿，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。目前正在进行研究导致这些变化的机制。

SCI

8 July 2022

Genetically Modified Porcine-to-Human Cardiac Xenotransplantation

(The New England Journal of Medicine, IF: 176.079)

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.

CORRESPONDENCE TO: bgriffith@som.umaryland.edu, mmohiuddin@som.umaryland.edu

SUMMARY 摘要

A 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Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60.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.)

一位57岁的非缺血性心肌病患者，此前处于依赖体外膜肺氧合（ECMO）中，无法应用标准治疗方法（包括传统同种异体移植），获得了一只具有10个单独基因编辑的转基因猪源动物心脏。基于CD40阻断进行免疫抑制。术后患者脱离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天出现突然舒张性增厚和衰竭，患者的生命支持在第60天停止。尸检发现异种移植物水肿，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。目前正在进行研究导致这些变化的机制。（由马里兰大学医学中心和医学院资助。）