The limited supply of donor organs has been a problem for several decades, and currently, there are over 100,000 individuals on the national transplant waiting list in the US. However, xenotransplantation can potentially reduce the shortage of access to organs. Within the last couple of years, there have been more research efforts focused on creating donor organs and grafts from pigs, involving editing out various genes using CRISPR and using non-human primates for trial. Utilizing knockout pigs has become advantageous because pigs reach reproductive maturity quickly and have anatomical organs similar to humans. Yet, there are physiologic differences in the functional and metabolic capabilities between human allografts and pig xenografts that must be accounted for. These differences include genetic protein structures and subsequent functions that can lead to graft incompatibility. Specifically, porcine lung, heart, pancreas, and kidney allografts can sustain life in non-human primates, while porcine livers have physiologic differences that cause life-threatening complications. Therefore, proper comparison and clinical analysis between recipients of xenografts and allografts are crucial to progress science further.
The first reported xenotransplant took place on January 7, 2022, at the University of Maryland, Baltimore involving a 10G-pig xenoheart transplant in a living human. During the early weeks after the transplant, the heart performed well in the absence of rejection. However, during the 8th week post-transplant, the patient’s status began to decline and he passed away from multiorgan failure. That said, hyperacute rejection was not the cause of his death, instead, the xenograft prolonged the life of this patient. Due to this, other xenotransplant trials began to be performed involving kidney transplantation. On September 24, 2021, Dr. Robert Montgomery transplanted a kidney from an alpha 1,3-galactosyltransferase gene-knockout pig into a brain-dead patient. This trial concluded that the kidney produced urine and clear creatinine while showing no hyperacute rejection. These trials, among others within the past years, have advanced the medical field and provided a promising solution for the organ shortage. While this is so, xenotransplantation has raised ethical concerns relating to human/animal welfare, hyperacute rejection, risk of infection, and the possibility of zoonotic disease transmission. Overall, xenotransplantation can potentially reduce the transplant waitlist while expanding the eligibility of transplants to more candidates. However, there is a need for more research and trials as well as the consideration of the social and ethical concerns with utilizing porcine organs for human life and benefits.
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ReplyDeleteThis is actually a topic in science that I find incredibly interesting. A lot of the foundation of this procedure depends a lot on therapeutic cloning. Cloning is a hot topic both in and out of the scientific world. For those that don't understand the science behind cloning, it is essentially when an oocyte is extracted with no nucleus. A nucleus from a somatic cell is extracted and placed into the oocyte where a chemical/electrical shock is given in order to fuse the nucleus and the egg together. The cell then develops into a blastocyst cell. Inside the blastocyst is an inner cell mass of stem cells and as you know these are pluripotent, they can become any cell in the body. Cloning played a major role in the development of xenotransplantation and plays a major role in how xenotransplantation works without rejection in humans. Xenotransplantation makes it so those that have organ transplants don't have to take drugs to prevent rejection because the organ has their DNA and is aligned with their immune system. The organ from the animal would also create human proteins. Unfortunately, as we read above, there has not been long term success with this method. I do believe with more advancement in this area there could be so much more that we could do with it but there are a lot of debates surrounding ethics, costs, and human/animal exploitation. Additionally, the advancement in this field underlying this procedure is largely under funded so in order to advance towards a possible long term transplant there needs to be discussion around advancing the technology unless you're against the use of animals for human gain which is also a very important topic to discuss. In my opinion, I think that the pigs and animals that are used for this are going to have a much better life as compared to a pig being grown for food. These animals will not be allowed to have any sort of antibiotics, they can not be stressed, the can not be mishandled in anyway shape or form, they would have a better life than most. Although like other pigs and animals they are still being used at the cost of their life for our gain.
ReplyDeleteGreat job on this blog post! I remember learning about this topic in the sophomore biology seminar with Dr. Streifel. While most of the class agreed that xenotransplantation is ethical, it was fascinating to discuss the opposing viewpoints. Given that many things can go wrong and ethical debates usually arise, it’s crucial to review the ethical implications at each major milestone. A question that comes to mind for me is how the public and patients awaiting organ transplants would respond to the concept of animal xenotransplantation. I know many patients are hesitant about bovine or porcine valve replacements, so I wonder how those on the transplant list, often viewing it as a last resort, would react. Would they be more willing to accept it, or would their reservations remain?
ReplyDeleteThanks for sharing this topic Denise! The topic of transplantation truly fascinates me as it mirrors what happens in science fiction. Even though the body needs the organ to survive, there is a chance that it will reject whatever organ it is because it is not self. I know that Major Histocompatibility Complex is what our body uses to determine self and I found that chimpanzees have the most similar MHC to ours from this paper (https://doi.org/10.1186/s12862-020-01669-6). I wonder how close pig hearts and other xenotransplantation organs are to human leukocyte antigens that it wouldn't reject the organ. Thanks for the post!
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