Postoperative lower limb ischemic necrosis following xenogeneic heart transplantation from gene-edited pigs to rhesus macaques
- VernacularTitle:基因编辑猪-猴异种心脏移植术后下肢缺血坏死
- Author:
Xianzhi WANG
1
;
Zhipeng REN
1
;
Ziqiang DAI
1
;
Rong ZHOU
2
;
Gen ZHANG
1
;
Jie YAN
3
;
Yulong GUAN
4
;
Guangyu PAN
5
;
Xingzhuang HE
6
;
Tingting LIU
6
;
Shangxuan LI
1
;
Guanzheng CUI
1
;
Chenghong LAI
7
;
Dengke PAN
3
;
Dianyuan LI
1
Author Information
1. Department of Cardiovascular Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215000, Jiangsu, P. R. China
2. Department of Ultrasound, First People's Hospital of Neijiang, Neijiang, 641000, Sichuan, P. R. China
3. Chengdu Aoge Biotechnology Co, Ltd., Chengdu, 610094, P. R. China
4. Extracorporeal Circulation Center, National Cardiovascular Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, P. R. China
5. Department of Cardiovascular Surgery, Peking University People's Hospital, Beijing, 100032, P. R. China
6. Department of Pathology, First People's Hospital of Guangyuan, Guangyuan, 628000, Sichuan, P. R. China
7. Medical Affairs Department, First People's Hospital of Neijiang, Neijiang, 641000, Sichuan, P. R. China
- Publication Type:Journal Article
- Keywords:
Gene editing;
xenotransplantation from gene-edited pigs to rhesus macaques;
heart transplantation;
lower extremity ischemia;
vascular thrombosis;
pathology;
imnunological rejection
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2026;33(09):1474-1481
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.
