HMN 2025: How Genetically modified pig lung functions in human body for 9 days

A genetically modified pig lung remained viable and functional over a period of 9 days after being transplanted into a human recipient who had been declared brain dead, according to research published in Nature Medicine. These findings may represent the first documented instance of cross-species lung transplantation and have potential future clinical applications, the authors suggest.

Xenotransplantation, which involves transplanting organs from one species into another, represents a potential solution to the shortage of human organs for transplantation. Previous studies have demonstrated the feasibility of transplanting kidneys, hearts and livers from gene-edited pigs into humans. However, the transplantation of lungs presents challenges distinct from the transplantation of other solid organs, owing to their anatomical and physiological complexity.

Jianxing He and colleagues transplanted the left lung of a gene-edited pig into a 39-year-old human recipient, who had been declared brain-dead by four clinical assessments, and monitored how the lung functioned and the human immune system responded. The pig from which the lung was obtained had undergone gene editing by CRISPR to remove the antigens that could activate the human immune system following the transplantation.

The authors found that the lung was not immediately rejected by the immune system and maintained viability and functionality over the course of 9 days. However, they observed signs of lung damage at 24 hours after transplantation and signs of antibody-mediated rejection of the lung at days 3 and 6 after transplantation, and the experiment was terminated on day 9.

The findings represent a first step towards pig-to-human lung transplantation. However, improvements are needed to optimize both the genetic modifications made in the donor pig and the immunosuppressive drugs needed to avoid immune-mediated rejection of the lung and to maintain long-term function, the authors conclude.