Repository: https://github.com/jinyancool/xenotransplantation Principal Investigator: Jhuanglab Contact: hiekeen [at] gmail.com
(Figure: Surgical success with immediate bile production followed by rapid consumptive coagulopathy and macrophage-driven innate response)
Liver xenotransplantation is the most promising strategy to solve the global shortage of donor livers. Although recent pig-to-human heart, kidney, and auxiliary liver transplants have proven surgical feasibility, coagulation dysregulation remains the major obstacle to long-term survival.
Here we performed orthotopic liver xenotransplantation from our specific pathogen-free (SPF) 10-gene-edited pig (GTKO/CMAHKO/β4GalNT2KO + hCD46/hCD55/hCD59/hTBM/hCD39/hEPCR/hCD47) into a Tibetan macaque. The graft showed immediate function (bile production within minutes) but the recipient rapidly developed severe consumptive coagulopathy with thrombocytopenia, fibrinogen depletion, PT/INR prolongation, and marked reduction of plasma von Willebrand factor (vWF) within 24 h.
These data reveal that, despite extensive genetic engineering, the principal early barriers in porcine-to-primate liver xenotransplantation are macrophage-driven innate immunity and systemic coagulation exhaustion via the complement–coagulation axis.
- Pig: Sus scrofa 11.1 (Sscrofa11.1)
- Macaque: Macaca mulatta (Mmul_10)
Keywords: liver xenotransplantation • liver transplantation • genetic engineering • multi-omics • coagulation dysregulation • macrophage activation • non-human primate • Tibetan macaque