Results of Two Cases of Pig-to-Human Kidney Xenotransplantation
Results of Two Cases of Pig-to-Human Kidney Xenotransplantation
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DOI：
10.1056/nejmoa2120238
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发表时间：
2022-05-19
影响因子：
158.5
通讯作者：
Stewart, Zoe A.
中科院分区：
文献类型：
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作者：
Montgomery, Robert A.;Stern, Jeffrey M.;Stewart, Zoe A.
转基因猪的异种移植已经成为解决可供移植的人体器官缺乏的最有希望的解决方案之一。该模型的挑战是超急性排斥反应。为了避免这一点，猪已培育敲除的α-1，3-半乳糖基转移酶基因和囊下自体thymic tissue.METHODSWe移植肾脏从这些转基因猪到两个脑死亡的人类受体，其循环和呼吸系统的活动是保持在呼吸机的研究期间。我们进行了一系列的活组织检查，并监测尿量和动力学估计的肾小球滤过率（eGFR），以评估肾功能和异种移植排斥反应。在54小时的研究中，动态eGFR从移植前的23 ml/min/1.73 m2体表面积增加到1991年移植后的62 ml/min/1.73 m2，1992年从55 ml/min/1.73 m2增加到109 ml/min/1.73 m2。在这两个受体中，一直处于稳定状态的肌酐水平在异种移植物植入后下降，在1991年从1.97 mg/dl下降到0.82 mg/dl，在1992年从1.10 mg/dl下降到0.57 mg/dl。移植的肾脏保持粉红色，灌注良好，在整个研究过程中继续排尿。在6、24、48和54小时进行的活检显示没有超急性或抗体介导的排斥反应的迹象。与异种移植每小时的尿量是两倍以上的输出与native kidneys. CONCLUSIONSSIGENTS转基因肾异种移植从猪脑死亡的人收件人仍然可行和功能为54小时，没有超急性排斥反应的迹象。
BACKGROUNDXenografts from genetically modified pigs have become one of the most promising solutions to the dearth of human organs available for transplantation. The challenge in this model has been hyperacute rejection. To avoid this, pigs have been bred with a knockout of the alpha-1,3-galactosyltransferase gene and with subcapsular autologous thymic tissue.METHODSWe transplanted kidneys from these genetically modified pigs into two brain-dead human recipients whose circulatory and respiratory activity was maintained on ventilators for the duration of the study. We performed serial biopsies and monitored the urine output and kinetic estimated glomerular filtration rate (eGFR) to assess renal function and xenograft rejection.RESULTSThe xenograft in both recipients began to make urine within moments after reperfusion. Over the 54-hour study, the kinetic eGFR increased from 23 ml per minute per 1.73 m(2) of body-surface area before transplantation to 62 ml per minute per 1.73 m(2) after transplantation in Recipient 1 and from 55 to 109 ml per minute per 1.73 m(2) in Recipient 2. In both recipients, the creatinine level, which had been at a steady state, decreased after implantation of the xenograft, from 1.97 to 0.82 mg per deciliter in Recipient 1 and from 1.10 to 0.57 mg per deciliter in Recipient 2. The transplanted kidneys remained pink and well-perfused, continuing to make urine throughout the study. Biopsies that were performed at 6, 24, 48, and 54 hours revealed no signs of hyperacute or antibody-mediated rejection. Hourly urine output with the xenograft was more than double the output with the native kidneys.CONCLUSIONSGenetically modified kidney xenografts from pigs remained viable and functioning in brain-dead human recipients for 54 hours, without signs of hyperacute rejection.