Clinical Pig Organ Transplantation: What Have We Learned So Far?

Since January 2022, eleven clinical xenotransplants into living patients involving gene-edited pig hearts (n = 2) or kidneys (n = 9) have provided initial data on patient selection, organ sourcing, and immunosuppression. Lessons from cardiac cases indicate that (i) patient selection must prioritize candidates with a realistic recovery potential from preexisting debility, (ii) immunosuppressive regimens should be initiated 5-7 days pretransplant to ensure therapeutic blood levels, (iii) the administration of products that potentially contain anti-pig antibodies should be avoided, and (iv) highly sensitive assays are essential to ensure the graft is free of pathogenic microorganisms. In renal cases, evidence suggests that (i) pig organs with multiple gene edits may provide superior protection against the human immune response, and (ii) while immunosuppression targeting the CD40/CD154 co-stimulation pathway effectively prevents the adaptive immune response, it currently fails to eliminate the development of thrombotic microangiopathy or proteinuria. It remains to be determined whether the current gene editing and immunosuppressive protocols are sufficient to enable truly long-term survival of patients and grafts.