biostudies-literatureShin HYInstitute of Civil-Military Technology Cooperation44014https://www.ebi.ac.uk/biostudies/studies/S-EPMC12711946biostudies-literatureUnknown15(1)To overcome cross-species immunological barriers, researchers utilize gene editing to remove the expression of three major carbohydrate xenoantigens (α-Gal, Neu5Gc, and Sd(a)) and insert genes, such as human protective genes (hCD55 and hCD39). This study aimed to investigate the mechanisms underlying long-term hepatic injury following xenotransfusion of genetically modified pig red blood cells (pRBCs). We xenotransfused pRBCs genetically engineered with GGTA1^-/-(α-Gal ^-); CMAH^-/-(Neu5Gc^-); β4GALNT2^-/-(Sd(a) ^-); hCD55; hCD39 into a non-human primate (NHP) model of acute hemorrhage hemolysis and evaluated the long-term immune response to xenogeneic RBCs in the liver, a key organ for RBC metabolism. Immediately after xenotransfScientific reportsHemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells.PMC1271194622-CM-EC-18Shin HYJang YJKo NKang GHPark SRKim HSLee JYShim JHwang JHfalseHemolysis-induced hepatic ferroptosis following xenotransfusion of genetically modified pig red blood cells.To overcome cross-species immunological barriers, researchers utilize gene editing to remove the expression of three major carbohydrate xenoantigens (α-Gal, Neu5Gc, and Sd(a)) and insert genes, such as human protective genes (hCD55 and hCD39). This study aimed to investigate the mechanisms underlying long-term hepatic injury following xenotransfusion of genetically modified pig red blood cells (pRBCs). We xenotransfused pRBCs genetically engineered with GGTA1^-/-(α-Gal ^-); CMAH^-/-(Neu5Gc^-); β4GALNT2^-/-(Sd(a) ^-); hCD55; hCD39 into a non-human primate (NHP) model of acute hemorrhage hemolysis and evaluated the long-term immune response to xenogeneic RBCs in the liver, a key organ for RBC metabolism. Immediately after xenotransf2025-01-01T00:00:00Z2025 Dec2026-06-10T05:18:21.803Z2026-06-10T03:07:39.969ZS-EPMC127119464140245410.1038/s41598-025-30021-5