China performs first pig-to-human lung transplant after brain death

Specialists at Guangzhou University Hospital performed the first lung transplant from a genetically modified pig to a brain-dead person.

The lung remained viable and functional, although it showed signs of damage and rejection.

The operation demonstrates the potential viability of the procedure, but significant challenges remain, the specialists explained in the study published in Natura Medicine .

Chinese researchers performed a xenotransplant at Guangzhou University Hospital, which involved transplanting a pig lung , which was genetically modified to facilitate compatibility with the patient.

Previous studies have demonstrated the feasibility of transplanting modified pig kidneys, hearts, and livers into humans, but lungs present different challenges due to their anatomical and physiological complexity.

The patient was a 39-year-old man declared brain dead after a hemorrhage in the brain .

The pig, for its part, underwent six gene editing using the CRISPR tool to eliminate antigens that could activate the human immune system.

Only the pig's left lung was transplanted, and the patient retained his right lung.

According to the article, the organ maintained its viability and functionality during the 216-hour (nine-day) follow-up period.

There were no immediate signs of hyperacute rejection or infection, “overcoming key barriers that have historically limited lung xenotransplantation.”

Although there was no initial organ rejection, signs of lung damage were observed 24 hours later.

The transplanted lung presented severe edema, similar to primary graft dysfunction, “possibly due to ischemia-reperfusion injury.”

This is damage caused when the blood supply returns to the tissue after a period of oxygen deprivation.

Therefore, the patient was placed on intensive immunosuppression and steroid therapy in increasing doses, with adjustments made during the postoperative period based on assessments of immune status .

Antibody-mediated rejection “appeared to contribute to xenograft damage” on days three and six after surgery, with partial recovery by day nine, the researchers write.

Although the study “demonstrates the feasibility” of pig-to-human lung xenotransplantation, the authors acknowledge that “significant challenges” remain.

These are related to organ rejection and infections, and further preclinical studies are needed before clinical translation of this procedure.

A key challenge in lung xenotransplantation is the high risk of infection, given that the direct interface of this organ with ambient air increases susceptibility to environmental pathogens.

Furthermore, the early onset of pulmonary edema underscores the importance of preventing primary graft dysfunction in future xenogeneic lung transplants.

The study, according to its authors, provides crucial information about the immunological, physiological, and genetic barriers that must be overcome, and paves the way for future innovations in this field.

“ Apart from demonstrating that it can be done, there are more unknowns than answers derived from this study ,” said Rafael Matesanz , founder of the National Transplant Organization in Spain .

The researcher, who did not participate in the study, said that since the patient retained one of his lungs in good condition, "assessing the functional evolution of the graft is complicated," but the line of research must continue.

“ The possibility of achieving good development of one of these lungs in a patient, with acceptable survival, seems remote and, of course, much more complicated than in the case of a kidney or liver .”

This first lung xenotransplant, he said, “opens a small door to the world of xenotransplantation, but with many more questions than answers.”