Update: Are Pig Kidneys the Future of Transplant Medicine?
The NYU Langone Transplant Institute team concluded its study of a transplanted genetically engineered pig kidney into a human
Introduction:
In a previous article, we discussed a pioneering clinical study from NYU Langone Transplant Institute that has the potential to revolutionize organ transplantation through the use of genetically modified donor animals (the original post can be found here). The study's leaders proposed that by knocking out alpha-gal—a key immunogenic marker—organs derived from animals could be rendered less prone to rejection after transplantation. My previous article unpacked the innovative strategies that enabled this study, including the theory behind alpha-gal immune activation, the genetic alteration of pigs to eliminate this cell surface marker, and the subsequent transplantation of a pig kidney and thymus into a human patient. However, the study was still ongoing as of the original post. With the study reaching its conclusion, this article will provide an update on the outcomes and reflect on their implications for the future of organ transplantation.
Kidney transplant procedure:
The xenotransplant conducted on July 14, 2023, marked a significant milestone in medical science. It involved transplanting a kidney and thymus from a GalSafe™ pig, a genetically modified animal developed by Revivicor, Inc., part of United Therapeutics Corporation. These pigs, approved by the FDA for both human therapeutics and consumption, are designed to eliminate the alpha-gal sugar molecule, addressing alpha-gal syndrome—a novel meat allergy triggered by a tick bite.
The recipient of this transplant was a 58-year-old man who had been declared brain-dead and was maintained on a ventilator. With the consent of his family, who wished to contribute to this groundbreaking research, the procedure was carried out. This study, a duration of two months, was pivotal in assessing the compatibility and functionality of the GalSafe pig kidney in a human body, representing a significant step forward in the field of xenotransplantation.
Preliminary Findings:
The study reached its conclusion after an extended duration of 61 days, surpassing the initially planned one-month period. This extension was crucial for gathering more comprehensive data. Remarkably, the transplanted kidney functioned effectively throughout the study, setting a record for the longest functioning period in such research. The team closely monitored the kidney for signs of functionality and immune rejection.
At the end of the study, the kidney was removed for detailed analysis, with approximately 180 tissue samples collected to investigate potential impacts on other organs. The success of the transplant is largely attributed to the genetic modification of the donor pig, specifically the elimination of the alpha-gal molecule gene, known to trigger rapid rejection of pig organs in humans. Additionally, the fusion of the pig's thymus gland with the kidney was a strategic move to mitigate delayed immune responses.
However, the study did observe some early signs of rejection, identified as a reduction in urine and other “novel cellular changes.” These were managed with increased immunosuppression, allowing the study to reach its full term. The research team is now analyzing the data to understand these cellular and molecular changes in depth. This analysis is vital for both recognizing the achievements of the study and identifying areas for improvement in xenogeneic organ compatibility. Notably, while other studies have involved knocking out multiple genes to reduce immunogenicity, the success of this study with a single gene knockout is particularly remarkable and paves the way for future advancements in the field.
Conclusions and what comes next:
Xenotransplantation has seen numerous attempts at pig organ transplants over the years, each contributing incrementally to our understanding but often met with limited success. This latest study from NYU Langone Transplant Institute represents a significant advancement in enhancing xenogenic organ compatibility. The comprehensive findings from this study, eagerly awaited by the scientific and medical communities, are expected to be published in the coming months. These insights will undoubtedly fuel further research and experimentation in the field.
While this study has achieved a remarkable feat, it also highlights that overcoming the challenges of xenotransplantation extends beyond addressing the alpha-gal barrier alone. It underscores the complexity of organ compatibility and the need for continued innovation. Nonetheless, this achievement is a critical step towards alleviating the organ shortage crisis, offering a glimmer of hope for the 104,000 patients on the US organ transplant list.
I will watch for any significant updates as this fascinating medical science journey unfolds.
References:
https://www.nature.com/articles/d41591-023-00078-8
NYU Langone Health Multimedia materials - available for download.
Extremely interesting first step, one that suggests that there is quite a long way yet to go before the rejection issue is resolved. {And as a non-medical person, I though that the procedure used was somewhat creepy, even though all ethical norms were observed. )
Very interesting article about a promising application of gene editing technology.
Still, researchers keep trying to force the square peg of xenotransplantation into the round hole of human biology. Wouldn't it be easier, faster, and make more sense to remove one of the biggest barriers to organ shortages by letting people sell them? Thousands of people on transplant lists die every year, deaths that might very well be prevented if the prohibition on sales were lifted. Of course as soon as you say that people assume that orphans will be selling their hearts on street corners, but there's no reason for that to be the case, especially if the sold organs had to come from patients declared legally dead, just as donated organs do. And when it comes to being not-for-the-squeamish, how is signing a card to authorize the post mortem sale of your heart any creepier than keeping someone on life support for a month so he can be experimented on? The researchers' experimentation was handled ethically and, I imagine, with kindness toward the family that approved it. The sale of a brain-dead patient's organs wouldn't be any different. Better, in fact: If the seller had designated the sale in advance, in writing, just as people do now with donations, then the "organ seller card" could specify who benefited from the sale: a charity, a family member, the person's estate; it could be applied toward the deceased's funeral expenses or hospital bill. That additional financial incentive might be enough to convince another 6,000 Americans to sign up for the program: enough to save the 6,000 people who die on waiting lists every year.