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BMC Kidney Transplant Director Discusses Groundbreaking Pig Kidney Surgery at Massachusetts General Hospital
On average 17 people People die every day in the United States waiting for an organ transplant. Could patients and doctors use animal organs to save lives?
The enticing prospect came after a 62-year-old man with end-stage renal disease underwent a pig kidney transplant at Massachusetts General Hospital in March. Died The hospital claims there is no evidence his death was related to the transplant, but nearly two months later the kidney was replaced. Genetically edited This is to remove harmful pig genes and add human genes.
BU Today Asked Jean FrancisWe spoke to Francis, an associate professor of medicine at Boston University's Chobanian-Avedisian School of Medicine, who also serves as medical director of the kidney transplant program at Boston Medical Center (the school's teaching hospital and the largest safety-net hospital in New England) and medical director of the pancreas transplant program at Brigham and Women's Hospital in Boston, about the current state of the field.
This interview has been edited for clarity and brevity.
question&a
Jean Francis and
BU Today: Which organs, and which animal organs, are most likely to be successfully transplanted into humans? Are any of these animal organ transplants in clinical trials?
Francis: So far, very limited trials have been done using only pig organs. The organs tested were hearts and kidneys. At the University of Maryland, two patients underwent heart transplants under very strict immunosuppressive therapy. One heart transplant lasted just over 40 days, the other nearly two months. Both hearts were eventually rejected (this is still up for debate), but both patients died after the transplants failed. This was one of the first trials to show the feasibility of such transplants and give clinicians an idea of what to expect in terms of complications.
The New York City program has two potential [terminal] “The pig kidneys were connected to the radial artery in the forearm and the patient was placed on life support for two days before being taken off the treatment. Neither kidney showed any signs of rejection and was still producing urine. As a proof of concept, they were able to show that future transplants like this would not experience hyperacute rejection.”
As a result of these studies, the MGH group recently received its first kidney transplant from a deceased donor and is moving forward with the first pig-to-human kidney transplant procedure in a patient who had been on dialysis for several years.
At present, the only animals that can be potential donors for human organ transplants are pigs. These animals have been genetically engineered to be compatible with humans. Further refinements of these modifications are constantly being revised. Currently, there are over 100,000 patients on the kidney transplant list. [in the United States]Nearly 5,000 patients die each year while waiting for a kidney donor. If modified pig kidneys prove effective, they could eliminate the organ shortage and waiting times. Well-organized, large-scale, multicenter trials confirming the benefits of such a procedure are needed before these organs can be widely used.
BU Today: Currently, what are the medical obstacles to successful animal-to-human transplantation?
Francis: The main obstacle is genetic compatibility. If pig kidneys are not genetically engineered, they will automatically reject the organ when transplanted. The kidneys need to be adapted for humans by removing or eliminating some of the antigens that are expressed on the lining of the blood vessels in the pig organ. Humans have already formed antibodies against these antigens, which cause acute rejection. These antigens are eliminated through genetic engineering.
Other modifications are also needed to make these organs less susceptible to inducing clotting and more resistant to the powerful human immune system, called the complement system. Complement activity must be controlled to prevent damage to the pig grafts. These pig organs are protected from complement damage by special drugs administered at the time of transplantation. Also, genetic modifications of these pig organs make them more resistant to complement attack and damage.
Finally, pig organs come to us with endogenous viruses that are part of the pig's genetic material. Although genetic engineering has allowed us to eliminate some of the pig retroviruses, we don't know if others still remain. So close monitoring for transmission from pigs to human recipients is also a concern, but so far the data supports safety in those very limited cases.
I am very optimistic that pig transplants will become available to many patients who have no other options. I feel this is the future of transplantation, a moonshot.
BU Today: Does Suleiman's death affect your optimism about pig organ transplants?
The unfortunate death of Mr Suleiman should not affect our determination to move forward. XenotransplantationNotably, so far there is no indication that the cause of his death was due to the pig's kidney. This is based on information released by the treatment team. Mr. Suleyman decided to become the first candidate to receive such a kidney, out of a desire to contribute to the development of this field. I am happy that Mr. Suleyman [would] We do not want his death to prevent the achievement of his wish to make xenotransplantation possible.
Every precaution must be taken to prevent future complications, and while it will take a long time to fully understand all the issues associated with xenotransplantation, we must be determined to continue advancing this field for patients until it is available to the masses.
I am very optimistic that pig transplants will become available to many patients who have no other options. I feel this is the future of transplantation, a moonshot. This will only happen after rigorous studies supporting safety, patient and organ survival, and optimization of artificial organs. Stay tuned.
