Preliminary attempts of establishing a transgenic pig-to-monkey orthotopic liver xenotransplantation model
10.3760/cma.j.cn421203-20230227-00043
- VernacularTitle:建立转基因猪-猴异种原位全肝移植模型的初步尝试
- Author:
Ting LI
1
;
Jiequn LI
;
Qiang LI
;
Zhongqiang ZHANG
;
Bin XIE
;
Hongjiang WEI
;
Zhongzhou SI
;
Haizhi QI
Author Information
1. 中南大学湘雅二医院肝脏移植科，移植医学研究中心，长沙 410011
- Keywords:
Xenotransplantation;
Liver transplantation;
Animal model
- From:
Chinese Journal of Organ Transplantation
2023;44(9):549-555
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the feasibility of a stable pig-to-monkey orthotopic liver transplantation (LT) model and provide a favorable experimental tool for preclinical studies of xenotransplantation.Methods:In this retrospective analysis, the authors reviewed the perioperative conditions and outcomes of 7 pig-to-monkey orthotopic liver transplants performed by a xenotransplantation research team of Second Xiangya Hospital.Gene-edited Banna miniature pigs were selected as donors and rhesus monkeys with similar anatomical characteristics, physiology, biochemistry and immune mechanism to humans were selected as recipients for pig-monkey xenogeneic orthotopic LT.Based upon classic transplantation procedures, whole liver xenogeneic orthotopic transplantation was performed.Surgical processes were modified for minimizing intraoperative hemorrhage and shortening anhepatic period.A bile duct drainage tube was implanted for observing bile secretion.ATG + anti-CD20 + snake venom factor and FK-506 were utilized for immunoinduction pre-operation while tacrolimus, mycophenolate mofetil (MMF) and methyl prednisolone for postoperative immunomaintenance therapy.Antibiotics and antiviral agents were also applied and thrombin complex for improving coagulation functions.Results:All procedures were successfully completed.After the stability and maturity of our model, in case No.7, donor's acquisition operative duration was 42 min without heat ischemic time, donor's trimming time 87 min, donor cold retention time 128 min, recipient's operative duration 123 min and anhepatic phase 27 min.Subhepatic inferior vena cava was occluded for 38 min.Blood loss was around 10 ml.And 4/7 models survived post-operation and the longest survival time was 27 h. Among 3 non-survival cases, the causes were anesthesia accident (n=1) and immaturity of early operation (n=2). Model No.7 had a biliary secretion volume of 86 ml post-operation.Conclusions:Qualified donor acquisition, high-quality vascular anastomosis, intraoperative reduction of blood loss, shortening of anhepatic period, strict fluid replenishing and careful monitoring are essential for boosting the success rate of pig-monkey liver xenotransplantation model.Optimization of donor gene combination and advanced immunosuppression protocol help to further achieve the long-term survival of pig-monkey liver xenotransplantation model.
