Two genetically modified pig kidneys have been successfully transplanted into a brain-dead human recipient, proving for the first time non-human renal organs can be adapted for use in patients in need of a transplant.
The team at The University of Alabama, Birmingham, say they are now preparing for a clinical trial involving living human recipients, to see if this approach as a potential solution to the current lack of available transplant organs.
Putting non-human organs into human recipients is called xenotransplantation, and has already been demonstrated in two previous experiments with pig kidneys.
However, writing in The American Journal of Transplantation, the researchers behind this latest study explain that theirs is the first to do so using a clinical-grade organ suitable for direct therapeutic use in living patients.
One of the biggest obstacles to xenotransplantation revolves around the fact that our immune systems are primed to identify and reject foreign material. To get around this, previous experiments have used pig kidneys genetically modified to lack a sugar molecule called alpha-gal, found on the surface of porcine organs and is easily recognized as alien by the human body.
While this prevented the rejection of the kidneys for up to 54 hours, researchers have now improved upon this approach by introducing ten different genetic modifications into the organs, similar to how a pig heart was recently modified for transplantation into a human.
These edits resulted in the loss of three pig carbohydrate antigens plus the pig growth hormone receptor gene. In addition, a number of human anticoagulant and immunoregulatory genes were inserted, thus rendering the kidneys more compatible with the human body.
The modified kidneys were transplanted into a 57-year-old brain-dead patient named Jim Parsons, whose family gave doctors permission to perform the procedure after he had a dirt bike accident. According to the study authors, the organs were not rejected by the patient’s body and remained viable for a full 77 hours.
Importantly, they also noted that the blood vessels in the kidneys were able to successfully withstand human blood pressure, which is significantly higher than that of pigs, and that no pig cells or viruses were detected in Parsons’s blood.
Ultimately, the purpose of this study was to develop a pre-clinical model of xenotransplantation to test the safety and feasibility of the approach, thus paving the way for future clinical trials. The idea was not, therefore, to optimize kidney function, yet the researchers were nonetheless able to confirm that urine output was “robust” from the right kidney, though less so from the left.
“The kidney turned beautiful and pink […] and within 23 minutes, it started making urine,” explained lead surgeon Jayme Locke in a statement.
There is still a long way to go before xenotransplantation can be applied to actual patients, yet the researchers are hopeful that their work could one day lead to a major increase in the availability of life-saving organs. “The concept of being able to have literally an organ waiting on the shelf, that is just waiting there for the person who needs it, is just overwhelming to think about, and exciting for them,” said Locke.
Parsons’s ex-wife Julie O’Hara added, “Jim would have wanted to save as many people as he could with his death, and if he knew he could potentially save thousands and thousands of people by doing this, he would have had no hesitation.”
“Our dream is that no other person dies waiting for a kidney, and we know that Jim is very proud that his death could potentially bring so much hope to others.”