Pig-to-human kidney xenotransplants using genetically modified minipigs
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, β4GalNT2, 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.
Authors
- Mingfa Wang (ORCID: https://orcid.org/0000-0002-9576-3283)
- Jiaxiang Du (ORCID: https://orcid.org/0009-0005-3798-284X)
- Jianli Wang
- Li Tao (ORCID: https://orcid.org/0000-0002-1874-1910)
- Songzhe He (ORCID: https://orcid.org/0009-0004-5022-1351)
- Huanliang Wang (ORCID: https://orcid.org/0000-0002-0109-5473)
- Man Zhang (ORCID: https://orcid.org/0009-0007-4481-0514)
- Yi Wang (ORCID: https://orcid.org/0000-0003-2455-2988)
- Gang Chen (ORCID: https://orcid.org/0000-0002-9989-2381)
- Kang Zhang (ORCID: https://orcid.org/0000-0003-3802-7535)
- Lili Liu (ORCID: https://orcid.org/0000-0001-9657-0857)
- Yong Wang (ORCID: https://orcid.org/0000-0003-0989-9764)
- Desheng Li (ORCID: https://orcid.org/0000-0002-4367-860X)
- Yong You (ORCID: https://orcid.org/0000-0002-4689-0235)
- Meng Yang (ORCID: https://orcid.org/0000-0001-6439-2873)
- Liang Xu (ORCID: https://orcid.org/0000-0002-0899-5669)
- Hang Yu (ORCID: https://orcid.org/0009-0002-4164-6433)
- H. Pei (ORCID: https://orcid.org/0000-0002-5078-3336)
- Hongtao Jiang
- Hui Guo (ORCID: https://orcid.org/0000-0001-8442-6487)
- Huiling Gan
- Quan Wen
- Bing Li (ORCID: https://orcid.org/0000-0002-5853-641X)
- Yifan Yu
- Shen Zhou
- Dengke Pan
- Zhonghua K Chen
- Zhian Song
- Hao Feng (ORCID: https://orcid.org/0000-0002-7493-766X)
Institutions
- Macau University of Science and Technology (MO)
- Huazhong University of Science and Technology (CN)
- Hainan Medical University (CN)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101744
- Citations
- 39
- Primary Topic
- Xenotransplantation and immune response
- Type
- article
- Field-Weighted Citation Impact
- 22.34