Pig-to-human kidney xenotransplants using genetically modified minipigs

被引：4

作者：

Wang, Yi ^{[1
,2
]}

Chen, Gang ^{[3
,4
]}

Pan, Dengke ^{[5
]}

Guo, Hui ^{[3
,4
]}

Jiang, Hongtao ^{[1
,2
]}

Wang, Jianli ^{[1
,2
]}

Feng, Hao ^{[3
,4
]}

He, Songzhe ^{[1
,2
]}

Du, Jiaxiang ^{[5
]}

Zhang, Man ^{[3
,4
]}

Li, Tao ^{[1
,2
]}

Wang, Yong ^{[5
]}

Yu, Hang ^{[1
,2
]}

Gan, Huiling ^{[1
,2
]}

Wen, Quan ^{[1
,2
]}

Song, Zhian ^{[1
,2
]}

Li, Desheng ^{[1
,2
]}

Yu, Yifan ^{[1
,2
]}

Wang, Huanliang ^{[1
,2
]}

Li, Bing ^{[1
,2
]}

You, Yong ^{[1
,2
]}

Zhou, Shen ^{[1
,2
]}

Wang, Mingfa ^{[1
,2
]}

Liu, Lili ^{[1
,2
]}

Xu, Liang ^{[1
,2
]}

Yang, Meng ^{[1
,2
]}

Pei, Hua ^{[1
,2
]}

Zhang, Kang ^{[6
,7
]}

Chen, Zhonghua K. ^{[3
,4
]}

机构：

[1] Hainan Med Univ, Affiliated Hosp 2, Hainan, Peoples R China

[2] Hainan Med Univ, Transplantat Inst, Hainan, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Organ Transplantat, Wuhan, Peoples R China

[4] Huazhong Univ Sci & Technol, Chinese Acad Med Sci, Key Lab Organ Transplantat,Minist Educ, NHC Key Lab Organ Transplantat, Wuhan, Peoples R China

[5] Chengdu Clonorgan Biotechnol Co Ltd, Chengdu, Peoples R China

[6] Macau Univ Sci & Technol, Inst AI Med, Macau, Peoples R China

[7] Macau Univ Sci & Technol, Fac Med, Macau, Peoples R China

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 10期

基金：

中国国家自然科学基金;

关键词：

ANTIBODIES; REJECTION; ANTIGENS; SURVIVAL; BABOONS;

D O I：

10.1016/j.xcrm.2024.101744

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, b4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/ hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

引用

页数：19

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