Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation

Yang Shujun; Wei Hao; Xu Yong; Wang Heng'en; Song Xiangyu; Jia Zhibo; Peng Jiang; Cui Mengyi; Yang Boyao; Chen Leijia; Guo Aitao; Zhang Xiaoli; Pan Dengke; Du Jiaxiang; Shang Panfeng; Sun Shengkun

doi:10.3969/j.issn.1674-7445.2023.04.008

Volume 14 Issue 4

Jul. 2023

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Yang Shujun, Wei Hao, Xu Yong, et al. Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation[J]. ORGAN TRANSPLANTATION, 2023, 14(4): 521-528. doi: 10.3969/j.issn.1674-7445.2023.04.008

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Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation

doi: 10.3969/j.issn.1674-7445.2023.04.008

Department of Urology, Second Hospital of Lanzhou University, the Second Clinical Medical College of Lanzhou University, Lanzhou 730030, China

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Corresponding author: Shang Panfeng, Email: shangpf@lzu.edu.cn; Sun Shengkun, Email: sunshengkun@301hospital.com.cn
Received Date: 2023-04-04
Available Online: 2023-07-13
Publish Date: 2023-07-15

Abstract

Abstract

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K⁺ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β₂-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.
- Xenotransplantation,
- Kidney transplantation,
- Gene-edited pig,
- Cynomolgus monkey,
- Rejection,
- α-1, 3-galactosyltransferase,
- β-1, 4 N-acetylg alactosaminyltransferase 2,
- Complement regulatory protein

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References(35)

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Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation

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Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation

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