First-in-Human, Open-Label, Within-Patient Controlled Study to Evaluate an Extensively Humanized Porcine Donor

Recent human decedent model studies and compassionate xenograft use have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation, and long-term life-supporting function of organs from selectively germline genome-edited pigs (SGGEP) with 11 genomic modifications. These modifications eliminated glycan xenoantigens, overexpressed human transgenes, and enhanced immunological and coagulation compatibility with human biology. In vitro analyses showed SGGEP cells possessed immunological tolerance and coagulation compatibility similar to human cells. In nonhuman primate models, kidney grafts sustained function for 447 days, and cardiac grafts survived healthily for at least 160 days. Skin grafts demonstrated life-supporting capabilities in a lethal skin removal model, facilitating complete wound closure and promoting autologous skin regeneration, remaining viable for ≥25 days without immune suppression. A clinical trial involving 31 patients with thermal burns showed that SGGEP skin grafts achieved complete and durable wound closure, with three cases not requiring autografting. These findings underscore the potential of SGGEP xenotransplantation in addressing donor organ scarcity and highlight the "one pig fits all" strategy as a promising solution for broader applications in human transplantation.