biostudies-literatureUnknown5(10)Wang YThis 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 pCell reports. Medicine101744https://www.ebi.ac.uk/biostudies/studies/S-EPMC11513830biostudies-literaturePig-to-human kidney xenotransplants using genetically modified minipigs.PMC11513830Liu LZhang KJiang HWen QZhang MGan HPei HWang HWang JYu HWang MGuo HChen ZKLi BWang YSong ZYu YXu LYou YLi DZhou SYang MChen GHe SPan DLi TFeng HDu JfalsePig-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 p2024-01-01T00:00:00Z2024 Oct2026-07-15T14:46:13.531Z2026-07-06T03:08:41.864ZS-EPMC115138303931719010.1016/j.xcrm.2024.101744