Is the First Pig-to-Human Liver Transplant a Success?
Xenotransplant recipient is doing well
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A 71-year-old man in China has become the first living recipient of a liver transplant — from a pig. This eight-hour surgery is a medical achievement in xenotransplantation—the transplanting organs or tissues between different species. More than two weeks post-surgery, the recipient is reportedly "doing very well," according to Sun Beicheng, the lead surgeon at the First Affiliated Hospital of Anhui Medical University. This success is a triumph for the patient and a symbol of hope for those awaiting transplants.
The Journey to This Medical Milestone
Xenotransplantation from animals to humans has been a longstanding goal. However, major advancements are only recent. Since early 2022, various teams of surgeons have transplanted pig hearts, kidneys, and even a thymus into human patients. While some recipients have not survived long-term, often due to pre-existing health conditions, each procedure has provided invaluable insights into the feasibility and challenges of xenotransplantation.
Previous attempts this year included a U.S. team that connected a genetically modified pig liver to a clinically dead person outside their body in January and a Chinese team that transplanted a pig liver into another clinically dead individual in March. These procedures laid the groundwork for the successful transplantation into a living patient, demonstrating improved techniques and understanding of organ rejection.
The Genomics Behind the Transplant
The recipient of this latest procedure had a large tumor on the right lobe of his liver. As a result, he was ineligible for a human liver transplant due to the poor condition of his liver. The tumor posed an imminent threat, with the potential to rupture at any moment. Faced with limited options, the patient and his family opted for the experimental xenotransplant after first getting approval from the hospital's ethics and transplantation committees.
The pig used in this surgery was not an ordinary animal but a product of genetic engineering. The 514-gram liver came from an 11-month-old miniature pig weighing 32 kilograms. This pig had undergone ten genetic modifications to reduce the likelihood of organ rejection. Specifically, three genes involved in producing sugars that trigger the human immune response were deactivated, and seven human genes were introduced to help the pig's liver function more compatibly in the human body.
One of the critical aspects of this procedure was ensuring the pig liver was free from porcine cytomegalovirus, a virus linked to complications in previous xenotransplant cases. The absence of this virus, confirmed through rigorous testing, likely contributed to the initial success of the transplant.
Post-Operative Progress and Observations
The immediate results post-surgery were promising. As soon as blood flow was re-established, the pig liver began secreting bile, a crucial function for digestion and liver health. Bile production, which started at 10 milliliters on the first day, increased steadily to 200-300 milliliters by day 13. Although this is still below the average of 400 milliliters per day produced by a healthy human liver, it indicated that the organ was functioning and not being rejected.
A biopsy conducted on day 12 showed no signs of rejection, and the patient's liver function appeared normal. This outcome is particularly encouraging because livers experience less rejection and injury than other organs like kidneys, hearts, or lungs. However, experts, including Jay Fishman from Massachusetts General Hospital, caution that signs of chronic rejection could still emerge over time.
Interestingly, the pig liver also produced pig versions of essential proteins such as albumin and coagulation factors. Understanding how these proteins function in the human body could provide crucial insights for future transplants. If the pig proteins do not adequately meet the recipient's needs, researchers may need to further genetically modify pigs to produce human versions of these proteins.
The Future of Xenotransplantation
This successful transplant offers a lifeline to the recipient and serves as a vital learning opportunity for the medical community. As Sun Beicheng and his team monitor the patient's progress, they remain hopeful that the individual's left liver lobe will grow sufficiently to sustain full liver function. The pig liver is intended as a temporary bridge to support the patient until this natural regeneration occurs.
The potential of xenotransplantation to address the organ shortage crisis is immense. Each year, thousands of patients die while waiting for a suitable donor organ. By harnessing the capabilities of genetically modified pigs, researchers hope to create a reliable and sustainable source of organ transplantation. This could revolutionize the field of organ transplantation, reducing wait times and saving countless lives.
Ethical Considerations and Regulatory Hurdles
While the scientific and medical advancements in xenotransplantation are promising, they are accompanied by significant ethical and regulatory challenges. Ensuring the safety and efficacy of these procedures is paramount, and extensive clinical trials and long-term studies are necessary to establish their viability. Additionally, the genetic modification of animals raises ethical questions about animal welfare and the implications of creating genetically engineered life forms for human benefit.
Regulatory bodies worldwide must develop frameworks to address these concerns, balancing the potential benefits to human health with ethical considerations. Public perception and acceptance of xenotransplantation will also be crucial in its future development and implementation.
Reference
https://www.nature.com/articles/d41586-024-01613-4