Guangzhou Medical University First Affiliated Hospital Xenogeneic Lung Transplant Research Selected as 2025 Nature Medicine Breakthrough

Background

Organ shortages have driven interest in xenotransplantation, the use of animal organs in humans. Lungs present unique challenges due to their exposure to air and pathogens, making them prone to rejection even in human-to-human transplants. Prior to this work, successful pig-to-human transplants had been reported for kidneys, hearts and livers, but lung xenotransplantation had not been documented in humans.

The research conducted by Jianxing He and Xin Xu at The First Affiliated Hospital of Guangzhou Medical University was selected by Nature Medicine as one of its major biomedical breakthroughs for 2025. The announcement highlighted the team's world-first gene-edited porcine-to-human lung xenotransplantation study performed in a brain-dead recipient. This provided data on human immune responses to a xenogeneic lung.

What was achieved

Jianxing He and Xin Xu's team performed the world's first reported gene-edited porcine-to-human lung xenotransplantation. A left lung from a six-gene-edited Bama miniature pig was transplanted into a 39-year-old brain-dead man who had suffered a brain hemorrhage and was confirmed brain dead by four independent clinical assessments, with written informed consent from the family. Over 216 hours (9 days) of monitoring, the xenograft maintained viability, ventilation and gas exchange without signs of hyperacute rejection or infection.

Edema was observed at 24 hours and signs of antibody-mediated rejection were noted on days 3 and 6, with some damage that showed partial recovery by day 9. The study was published in Nature Medicine (volume 31, pages 3388–3393) on 25 August 2025. The research was selected as one of the 2025 major biomedical breakthroughs.

How it works

In xenotransplantation, genetically modified pig organs are used to address human donor shortages. Pigs are selected because their organ size is comparable to humans. The donor pig, raised in a strictly controlled pathogen-free facility, underwent six CRISPR gene edits: three pig genes (GGTA1, CMAH and B4GALNT2) were knocked out to eliminate antigens that trigger strong human immune responses, and three human genes (CD46, CD55 and thrombomodulin) were inserted to help regulate the complement system, reduce inflammation and prevent abnormal clotting.

The left lung was transplanted into the brain-dead recipient in a procedure designed to simulate a standard clinical single-lung transplant, with the recipient's own right lung left in place. The recipient received immunosuppressive medications. Continuous monitoring included pulmonary function tests for oxygenation and compliance, blood gas analysis, imaging and assessment for immune markers, rejection and infection over the 216-hour period.

What it means for international patients

The study provides data that may support future development of xenotransplantation to address global shortages of lungs for patients with end-stage respiratory disease. The hospital has been designated as one of Guangdong Province's international medical services pilot hospitals and maintains an International Medical Department, with services for overseas patients in respiratory medicine and thoracic surgery.

International patients should directly contact the hospital to confirm current availability, eligibility criteria for any programs or trials, and developments in this research area, as xenotransplantation is not yet established as routine clinical care for living patients.

About the hospital

The First Affiliated Hospital of Guangzhou Medical University is a public Grade III Class A comprehensive teaching hospital located in Guangzhou, Guangdong Province, China. Founded in 1903, it is affiliated with Guangzhou Medical University and integrates medical treatment, teaching and scientific research across multiple campuses including Yanjiang and Datansha. It hosts the National Clinical Research Centre for Respiratory Disease and is part of the National Center for Respiratory Medicine.

It is recognized for expertise in respiratory medicine, thoracic surgery, organ transplantation (including lung transplants from human donors), critical care, urology and oncology. The hospital was included among the first batch of Guangdong international medical services pilot hospitals and offers dedicated services for international patients including at the Datansha campus.