在临床批准的免疫抑制剂药物作用下胎猪肾脏在成熟猴体内的发育情况
Tsuyoshi Takamura , Kenji Matsui , Naoto Matsumoto , Yatsumu Saito , Toshinari Fujimoto , Susumu Tajiri , Shuichiro Yamanaka , Kei Matsumoto , Akimitsu Kobayashi , Izumi Yamamoto , Hiroshi Sasaki , Haruyuki Hirayama , Hitomi Matsunari , Kazuaki Nakano , Hiroshi Nagashima , Akihiko Kiyoshi , Takao Kuroda , Makoto Inoue , Takeshi Miyawaki , Takashi Yokoo , Eiji Kobayashi
工程（英文） ›› 2022, Vol. 10 ›› Issue (3) : 65 -73.
在临床批准的免疫抑制剂药物作用下胎猪肾脏在成熟猴体内的发育情况
In Vivo Development of Fetal Pig Kidneys in Mature Monkeys Under Clinically Approved Immunosuppressant Drugs
在从猪到非人灵长类动物的肾脏异种移植中，仅使用临床批准的免疫抑制药物来控制免疫反应是困难的。此外，据我们所知，目前还没有关于使用胎猪作为肾脏供体的报道。本研究旨在比较新生猪和胎猪肾脏之间的移植排斥程度，以遗传未修饰的猪作为供体，将食蟹猴作为受体。切除受体食蟹猴的左肾，然后将在同一部位进行了血管吻合的新生猪和胎猪的肾脏移植到食蟹猴左肾腹膜。仅使用美国食品药品监督管理局批准的药物进行免疫抑制。将胎猪肾脏移植到食蟹猴的网膜和腹主动脉旁区域。随时间取样（每个实验取样两次），对移植组织的移植成活率和发育进行病理学检查。几周后，观察到血管吻合的新生猪肾脏在移植后出现急性排斥反应。尽管对食蟹猴和流入胎猪肾脏的受体血管给予相同的免疫抑制方案，但胎猪的肾脏仍免于排斥。猪-猴肾脏异种移植中胎猪肾脏的免疫原性低于新生猪肾脏。
Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotransplantation from pigs to nonhuman primates. Moreover, to the best of our knowledge, no reports exist on the use of fetal pigs as kidney donors. This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys, with genetically unmodified pigs as donors and cynomolgus monkeys as recipients. The left kidneys of the recipient monkeys were removed, followed by transplantation of neonatal as well as fetal pig kidneys, which had undergone vascular anastomosis at the same site, into the retroperitoneum. Immunosuppression was performed with only US Food and Drug Administration-approved drugs. The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys. Consequently, the engraftment and development of the transplanted tissues were pathologically examined by sampling over time (twice in each experiment). An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis. However, fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys. The immunogenicity of fetal kidneys in pig–monkey renal heterotransplantation was lower than that of neonatal kidneys.
Cynomolgus monkey / Pig / Kidney / Fetal kidney / Immunosuppression
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