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In Vivo Development of Fetal Pig Kidneys in Mature Monkeys under Clinically Approved Immunosuppressant Drugs

Engineering 2022年第3期8卷 65-73页

作者： 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 Division of Nephrology and Hypertension Department of Internal MedicineThe Jikei University School of MedicineTokyo 105-8461Japan Department of Urology The Jikei University School of MedicineTokyo 105-8461Japan Department of Plastic and Reconstructive Surgery The Jikei University School of MedicineTokyo 105-8461Japan Meiji University International Institute for Bio-Resource Research Kanagawa 214-8571Japan Sumitomo Dainippon Pharma Co. Ltd.Osaka-fu 564-0053Japan Department of Kidney Regenerative Medicine The Jikei University School of MedicineTokyo 105-8461Japan

Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation 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.

关键词： Cynomolgus monkey Pig Kidney Fetal kidney Immunosuppression

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