2022, Volume 10, Issue 3
Engineering >> 2022, Volume 10, Issue 3 doi: 10.1016/j.eng.2022.02.001
In Vivo Development of Fetal Pig Kidneys in Mature Monkeys Under Clinically Approved Immunosuppressant Drugs
a Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan
b Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
c Department of Plastic and Reconstructive Surgery, The Jikei University School of Medicine, Tokyo 105-8461, Japan
d Meiji University International Institute for Bio-Resource Research, Kanagawa 214-8571, Japan
e Sumitomo Dainippon Pharma Co., Ltd., Osaka-fu 564-0053, Japan
f Department of Kidney Regenerative Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan
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Abstract
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.
Keywords
Cynomolgus monkey ; Pig ; Kidney ; Fetal kidney ; Immunosuppression
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