In the first experiment, a Chinese doctor transplanted lungs from genetically modified pigs into brain dead.
Similar experiments involving brain-dead patients have been previously performed in the US, but have involved different pig organs such as the kidneys and heart, and previous experiments in China included pig liver. These experiments pave the path to pig organ transplantation on living human patients, but only a handful of the procedures have been performed so far.
A recent experiment, written on Monday (August 25) in Nature Medicine, took place in Guangzhou, China, involving a 39-year-old man who was declared brain dead before the procedure. According to the report, the team confirmed that the patient had brain dead through four different assessments and obtained written informed consent from the family.
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This is the first time a doctor has attempted to implant a lung from another species into a human. This is a procedure known as pulmonary xenograft.
“For our team, this achievement is a meaningful beginning,” Dr. Jiang Shi, a physician at the organ transplant department at Guangzhou Medical University’s first affiliated hospital, told Stat. “Lung xenografts present unique biological and technical challenges compared to other organs.” The purpose of this study was to investigate how the human immune system responds to such transplants. In other words, this technique is not yet ready for prime time for living patients. It is still under preclinical investigation.
Upon implantation, the pig’s lungs “maintained feasibility and functionality” for 9 days despite showing signs of rejection 24 hours after the procedure. The experiment was completed on day 9 at the request of the patient’s family. Reports do not know how long the lungs lasted, but the organ had been damaged by day 9.
Related: Can I transplant an organ multiple times?
“No one will sign up for a nine-day lung transplant,” Dr. Adam Griesmer, a senior member of the xenotransplant team at NYU Langone’s Transplant Institute, who is not involved in the procedure, told CNN. It said, “I think it’s very important to do these research. [in brain-dead people] “It cannot be assumed that an animal model fully reflects what happens to human recipients,” Griezmer added.
This experiment included pig lungs that were genetically modified using the gene editing technique CRISPR. The editorial was handled by a company called Clonorgan Biotechnology in Chengdu, China. Three of the PIG genes are ineffective, so that the proteins they encode do not activate the human immune system. Three human genes have also been added to make organs more tolerant to the human body.
In May 2024, the transplant team removed the pig’s left lung and implanted it into a brain dead patient who held the right lung. Immunosuppressants were introduced into the patient’s body one day before treatment and administered daily after surgery.
The patient’s body showed no signs of “overrejection.” This will occur if it occurs immediately after the implantation. The lungs made its first hump, but signs of rejection began to appear around the 24-hour mark marked by swelling and inflammation. The immune system produced antibodies to the organs by the third day after surgery, resulting in some damage to the lungs.
Researchers have suggested that future attempts in this type of experiment could not only block the action of specific immune cells, but also help suppress certain signaling molecules that cause inflammatory. Given that the lungs are constantly exposed to air from outside the body, they carry a great challenge as they carry a lot of proteins directed towards immune defense. This paradoxically makes it a simple target that the host immune system considers as a “foreign body.” Furthermore, tissues that exchange oxygen and carbon dioxide are very sensitive, so the immune attacks fired against them pack a punch.
Other questions remain about how to improve the approach and how well it works for living patients. For example, based on the current study, it is unclear how well the pig’s lungs supported the patient if Dr. Richard Pearson, a chest transplant surgeon at Massachusetts General Hospital, who was not involved in recent procedures, was removed from a life support aircraft.
“Future research can improve approaches to lung xenografting and approach clinical translation,” the study authors concluded. “This study provides important insights into the immune, physiological and genetic barriers that need to be overcome, paving the way for further innovation in this field.”
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