Morimoto Keita, Yamanaka Shuichiro, Yokoo Takashi
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
Kidney Applied Regenerative Medicine, Project Research Units, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
Pediatr Nephrol. 2025 Jan 30. doi: 10.1007/s00467-025-06664-x.
Patients with kidney failure require dialysis or kidney transplantation. Kidney transplantation offers great benefits, including reduced mortality; however, many patients who wish to undergo kidney transplantation are unable to do so due to a shortage of donor organs. This shortage is a global issue, and xenotransplantation has emerged as a potential solution. The history of xenotransplantation is characterized by overcoming the immunological challenge of hyperacute rejection. Recently, breakthroughs such as gene-edited pigs and novel immunosuppressants have successfully lowered rejection rates. Recent clinical studies have reported transplants in patients diagnosed with brain death, and in March 2024, a gene-edited pig kidney was transplanted into a patient with kidney failure at Massachusetts General Hospital, marking the first instance of a gene-edited xenotransplantation into a living patient. Our research focuses on applying xenotransplantation in pediatric and obstetric fields, specifically exploring fetal therapy using pig fetal kidneys. We have long been researching the development of a novel kidney replacement therapy involving the transplantation of fetal pig kidneys. Fetal pig kidneys have the advantage of not requiring vascular anastomosis and are less likely to be rejected compared to adult pig kidneys. Currently, we are advancing nonhuman primate studies aimed at clinical trials of pig fetal kidney transplant therapy for fetuses diagnosed with Potter syndrome, characterized by bilateral kidney agenesis. We sincerely hope that xenotransplantation will soon become a viable treatment option for adult, pediatric, and fetal patients with kidney failure.
肾衰竭患者需要透析或肾移植。肾移植有诸多益处，包括降低死亡率；然而，许多希望接受肾移植的患者因供体器官短缺而无法进行移植。这种短缺是一个全球性问题，异种移植已成为一种潜在的解决方案。异种移植的历史以克服超急性排斥的免疫挑战为特征。最近，基因编辑猪和新型免疫抑制剂等突破成功降低了排斥率。近期的临床研究报告了在脑死亡患者中的移植情况，2024年3月，一个基因编辑猪肾被移植到马萨诸塞州总医院的一名肾衰竭患者体内，这标志着基因编辑异种移植首次应用于活体患者。我们的研究重点是在儿科和产科领域应用异种移植，特别是探索使用猪胎儿肾脏进行胎儿治疗。我们长期以来一直在研究一种涉及移植猪胎儿肾脏的新型肾脏替代疗法的开发。猪胎儿肾脏具有无需血管吻合的优势，并且与成年猪肾脏相比，被排斥的可能性更小。目前，我们正在推进非人灵长类动物研究，旨在对被诊断患有波特综合征（以双侧肾缺如为特征）的胎儿进行猪胎儿肾移植治疗的临床试验。我们真诚地希望异种移植很快能成为成年、儿科和胎儿肾衰竭患者可行的治疗选择。
