Two Truths and a Lie: Xenotransplantation
The 2022 NSMC Internship is broken down into four rotations. One rotation is called Podcasting. There are two deliverables for that rotation:
Why Nephrology, a solo essay recorded as a podcast
Two Truths and a Lie, a group project that requires mixing multiple speakers, from multiple continents into a cohesive podcast.
Pod Three divided into two teams to complete the second deliverable, here is one of those teams.
Cast:
Priya Yenebere
Zac Cerra
Christel Wekon-Kemeni
Mo Ibrahim
References
Cooper, DKC. “A Brief History of Cross-Species Organ Transplantation.” Proceedings - Baylor University. Medical Center 25.1 (2012): 49–57. Web. DOI:10.1080/08998280.2012.11928783
Roux FA, Saï P, Deschamps JY. Xenotransfusions, past and present. Xenotransplantation. 2007;14(3):208-216. DOI:10.1111/j.1399-3089.2007.00404.x
Denner J. Porcine endogenous retroviruses (PERVs) and xenotransplantation: screening for transmission in several clinical trials and in experimental models using non-human primates. Ann Transplant. 2003;8(3):39-48. https://doi.org/10.1186/s12977-018-0411-8
Wijkstrom M, Iwase H, Paris W, Hara H, Ezzelarab M, Cooper DK. Renal xenotransplantation: experimental progress and clinical prospects. Kidney Int. 2017;91(4):790-796. DOI: 10.1016/j.kint.2016.08.035
Soin B, Smith KG, Zaidi A, et al. Physiological aspects of pig-to-primate renal xenotransplantation. Kidney Int. 2001;60(4):1592-1597. DOI: 10.1046/j.1523-1755.2001.00973.x
Iwase H, Liu H, Wijkstrom M, et al. Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date. Xenotransplantation. 2015;22(4):302-309. DOI: 10.1111/xen.12174
Cooper DKC, Wijkstrom M, Hariharan S, et al. Selection of Patients for Initial Clinical Trials of Solid Organ Xenotransplantation. Transplantation. 2017;101(7):1551-1558. DOI: 10.1097/TP.0000000000001582
Fishman JA. Infectious disease risks in xenotransplantation. Am J Transplant. 2018;18(8):1857-1864. DOI:10.1111/ajt.14725
Rosner F. Pig organs for transplantation into humans: a Jewish view. Mt Sinai J Med. 1999;66(5-6):314-319.
Mansour T. Azhar issues fatwa allowing transplant of pigs' kidneys. The New Arab. https://english.alaraby.co.uk/news/azhar-issues-fatwa-allowing-transplant-pigs-kidneys. Accessed July 3, 2022.
Lu T, Yang B, Wang R, Qin C. Xenotransplantation: Current Status in Preclinical Research. Front Immunol. 2020;10:3060. Published 2020 Jan 23. DOI:10.3389/fimmu.2019.03060
Carrier AN, Verma A, Mohiuddin M, et al. Xenotransplantation: A New Era. Front Immunol. 2022;13:900594. Published 2022 Jun 9. DOI:10.3389/fimmu.2022.900594
SCRIPT
Priya: What’s up everyone and welcome to our episode of Two Truths and a Lie a podcast hosted by the interns of the Nephrology Social Media Collective! My name is Priya Yenebere and I’m a transplant nephrologist at Indiana University in Indianapolis, Indiana and I am honored to be your host for today. Y’all have such a treat in store for you…because today’s topic has definitely created a lot of buzz in the nephrology world recently! Today, we are going to talk about xenotransplantation.
I hope you all are as excited as we are to get this episode going! So let's jump right and introduce each of our panelists to you.
Our first panelist today is Zac Cerra. Hey Zac, can you introduce yourself?
Zac: Hey everyone, my name is Zac Cerra and I am currently a 4th year student at McGovern Medical school at UT Health Science Center in Houston, Texas. I’m super pumped to be here, and excited to talk about our very interesting topic
Priya: Great! Thanks Zac. Our second panelist on today’s episode is Dr. Christel Wekon-Kemeni. Hey Dr. Wekon-Kemeni, can you please introduce yourself to our audience?
Christel: For sure! Hey everyone, my name is Christel Wekon-Kemeni, also known as “Dr. Dub”, and I’m currently a Chief Resident in the Department of Pediatrics at the University of North Carolina in Chapel Hill, North Carolina. I am both grateful and excited to be participating in this podcast with these marvelous people today! I do not have any conflicts of interest to declare!
Priya: Fantastic! Thanks Christel. And last but not least, our third panelist on today’s episode is Mohamed Ibrahim, can you introduce yourself?
Mo: Hi everyone, my name is Mohamed Ibrahim, I go by Dr. Mo, I am a kidney transplant physician and scientist at the University of Maryland in Baltimore. I am very excited to be with this amazing group today in the podcast.
Priya: Thanks you guys. So glad that we get to do this today - what a great group!
Ok everyone, so here’s how today’s episode is going to work: each of our panelists will present three statements - the catch is one of their statements is a lie! After a panelist presents, we will poll the group and hear their thoughts on which statement they think is the lie! For those of you playing at home, take a guess as well…and see if you are right. Once the polls close, our panelist will tell us how we did. All of these statements are very interesting, and the answers will definitely surprise you...I know that they surprised me!
So, without further ado,...let’s get started….Zac, do you want to start us off today?
Zac: Of course, Priya, looking forward to it! Here it goes:
Statement 1: There are documented attempts of xenotransplantation of all of the following organs into humans: Cornea, Heart, Liver, Kidneys, Skin, Testes, Blood, and Pancreatic islet cells
Statement 2: Attempts at xenotransplantation in humans date back to the 17th century
Statement 3: Endogenous retroviruses that are found in the genome of all porcine cells present a risk of infection to the recipient.
Priya: Oh wow - Zac, starting our show off really strong, because all of those sound like truths to me! I mean, with all the ongoing research in the field - I can only imagine that there have been attempts with all sorts of tissue, but come on…I don’t think all this started in the 17th century. I think that’s way too early, so I think number 2 is the lie. But let’s see what the group thinks. Christel - what are your thoughts?
Christel: I would honestly have to agree with you about statement #2 being the lie Priya. I can’t imagine anyone trying to transplant an organ from an animal into a human in the 1600s, ESPECIALLY since sterile surgery practices didn’t come into play until the late 1800s. I can see statement #1 being a truth due to the fact that there are a lot of medical conditions with pathologies in each of those organ systems, and it makes sense to me that researchers have been trying to get creative with finding ways to alleviate human suffering from those pathologies…though I’ll admit that the xenotransplantation of testes sounds a bit strange to me. Statement #3 sounds true to me too; it sounds intuitive to me that the cells of a non-human animal would have viruses and/or other organisms not native to humans that could potentially wreck havoc on the human immune system if allowed to. This would be a reason to carefully monitor patients with transplanted organs from animals, especially in the setting of immunosuppressive medications.
Priya: Ok ok, very interesting. And I like where you were going with statement 3, infection is always on the forefront of everyone’s mind when we think transplant between human recipient and donor. So, I’m sure there is a laundry list of potential infections that can arise when we are jump species. What about you Mo? Agree? Disagree?
Mo: Wow, I am really surprised about the testis xenotransplantation in statement 1. I know that the other tissue xenotransplants are true, however I am very curious to know if the testis xenotransplantation was really performed. So I would say the statement is probably a lie at least for the testis.
As far as statement 2, I think it is true, xenotransplantation was always envisioned even in the ancient times, for example the Sphinx in Egypt has a head of a human and a body of a lion, that’s one form of body xenotransplantation in my opinion!!
Now for statement number 3, I believe this is true too, because the recipient will be immunocompromised and this can lead to risk of infection with porcine retrovirus.
So curious to find the answers.
Priya: Well, I definitely agree with you guys, these are kinda tricky and Zac is definitely making us think good and hard about this. I think we might choose statement 2 as not being particularly truthful, not necessarily the concept being false, but the timeline. Zac, were we right?
Zac: So y’all had some great thoughts, I’m glad that I was able to generate some discussion! I’ll run through each statement now!
Statement 1 Explanation: My first statement about the different types of xenotransplanted grafts that have been attempted is TRUE. All of these have indeed been attempted in the past - obviously with limited success. I think of these, what was most shocking to me were the attempts by Dr. Voronoff to transplant chimpanzee and baboon testes into humans in an attempt to restore sex-drive in older men. This didn’t work out so well - he did, however, also perform the first human pancreatic islet cell transplants to treat patients with severe type I diabetes, although interestingly, we now know that this process requires the islet cells from 2-3 donors in order to be clinically effective (Cooper, 2012) . The history of skin xenograft transplant was also fascinating, as there were a variety of donor animals attempted (including sheep, dogs, cats, and pigeons) and some of the attempts at “pedicled” skin grafts (mostly attempted with sheep) involved keeping the donor immobilized and attached to the recipient for a period of several days. Corneal transplants with pig grafts are thought to be one of the most promising to become a reality in the near future, and there has been a lot of excitement surrounding the recent heart xenotransplant conducted at the University of Maryland. Unfortunately, the kidneys face some significant barriers for research as we have good therapies to bridge patients to allograft donation (hemodialysis), so ethically it is difficult to justify risky experimentation with xenotransplantation at this point.
Priya: Ok great. Sigh of relief, selfishly, I’m glad I didn’t get our first statement wrong! I know that we as a scientific community have been researching all sorts of tissues across all sorts of species. I guess in the kidney world where I live...we try and minimize exposure to different donors, say in combined liver-kidney or heart-kidney transplant, so I didn’t realize that you use multiple donors for islet cell transplantation. Ok, so we have researched all different kinds of tissues from an assortment of different animals, lets move on to your second statement. When did we start doing this?
Zac:
Statement 2 Explanation: So Priya, It is TRUE that xenotransplantation dates back to the 17th century. I’ll admit this one is a little tricky, since the first attempt at xenotransplantation was with blood products, of which the first documented cases were by Dr. Jean-Baptiste Denis of France in the late 1600s (Roux et. al., 2007) . I bring this up to highlight that humans have been thinking about xenotransplantation for a LONG time – dating back even to Greek mythology (Icarus and his bird-wings) - and, as Mo mentioned, the Sphinx in early Egypt (Cooper, 2012). First came blood, followed by skin grafts, but even as early as 1838, the first attempts at solid organ xenotransplant were made with corneal transplantation from donor pig grafts. I think it is pretty amazing to reflect back on how far we have come over the past 300+ years, but how we still have some work to do before xenotransplantation becomes a primetime reality.
Priya: Wow - that so interesting, and I think what you said is really eye opening. if you look back in time, whether it be in religion, folklore, or early science, there are all sorts of references to what we would now call - xenotransplantation. Mo mentioned the Egyptian sphinx earlier, but there other creatures in different cultures where this concept pops up: in Greek mythology, we have the minotaur: part man and part bull; centaurs: part human and part horse, seen in the ancient roman world, and even more recently in the beloved literary universe of Harry Potter. It seems that our civilization has always thought of this concept, but now we are looking at it through the eyes of science, as a possible solution to our global organ shortage crisis. I knew that research in the field of xenotransplantation has been going for a while, but I would have never guessed that it was that early in our history. Ok, so, I guess that if the first 2 were truths…that leaves us with our last statement.
Zac: Statement 3 Explanation: Right, Priya, so that means that my final statement about endogenous retroviruses in pigs posing an infectious risk to humans is my LIE. Interestingly, there are retroviruses found in almost all porcine cells, known as Porcine Endogenous Retroviruses or PERVs (Denner, 2018). These viruses are not pathogenic in pigs, but were originally thought to be potentially pathogenic in humans. However, there have been no documented instances of these viruses infecting human hosts to date. It is important to note though, that in these trials, weak or no immunosuppression was used, so there is concern that this possibility is not entirely ruled out. The lack of transmission is thought to be due to the lack of functional PERV receptors in recipient species. As of 2017, there were successful generations of live piglets in which PERVs are inactivated using CRISPR technology and continued work in this could help reduce this theoretical risk of PERV transmission to zero.
Zac: And with that, I’ll turn the mic back over to our host, Priya. I hope y’all found this as interesting as I did, and if you want some more reading on the history, check out our show notes with more information on the wonderful review article written by Dr. David Cooper.
Priya: Thanks Zac - wow, so your statement number 3 is the lie! Who would have guessed? It is definitely reassuring to know, that these retroviruses have been studied for a while, and that scientists are continuing to find ways to decrease what seems to be an already small risk of transmission. Again, lots of questions that pop up when we step into such a complex field of research.
OK! What a way to start the show - right at the very beginning with a small jump back in history to where this all started.
Ok, next up Dr. Wekon-Kemeni - you're up next. Why don’t you go ahead and share your statements with us.
Christel: I would be delighted to! My three statements are as follows:
Knocking out pig genes responsible for the expression of antigens that primates have natural antibodies against is the only way found thus far to protect pig kidney tissue from the primate immune response.
In the early studies of pig kidney xenotransplantation, moderate-to-severe proteinuria with resulting hypoalbuminemia were uniformly documented, which required frequent infusion of human albumin.
The FDA has suggested that xenotransplantation be limited to “patients with serious or life-threatening diseases for whom adequately safe and effective alternative therapies are not available”, while limiting the therapy to those patients “who have potential for a clinically significant improvement with increased quality of life following the procedure”.
Priya: Oh man, another good set of statements! All sort of focusing on the transplantation process and the science itself. Mo, tell me what you think about these three things? They all sound pretty good yea?
Mo: Wow, hard choices again, I am not very sure about the first statement, and I hope it is a lie, because I know that there are ongoing efforts to manipulate the immune system so that it will decrease the chances of rejection of xenotransplants. I think the second and third statements are true, the FDA is still very strict about the safety of xenotransplants.
Priya: I can definitely agree with your there Mo. The FDA has very strick rules in place when it comes to animal research in general, so I know that they are watching this field of research very closely. Zac, how about you? thoughts?
Zac: Hmm, I think that I’m gonna go with statement 2 as the lie - I’m sure in the early studies rejection was an issue, but surely we figured something out to keep the proteinuria to a more mild level. Guess we’ll find out though!
Priya: Nice point Zac. I’ll be honest, I’m sure that there was proteinuria, but im not entirely sure how much. So I think we all might have some differing opinions here Cristel. We agree that there are several different types of immunity our body uses when it comes to infection defense, and in today’s case - transplantation, but who knows how much proteinuria is actually coming out of these xenografts. So Dr. Wekon-Kemeni, why don’t you settle this for us? Which one of these is your lie?
Christel: Absolutely! The lie was statement #1, which was: Knocking out pig genes responsible for the expression of antigens that primates have natural antibodies against is the only way found thus far to protect pig kidney tissue from the primate immune response.
Statement 1 Explanation: This statement was a lie because while it is true that we can knockout pig genes responsible for antigen expression that primates have natural preformed antibodies against, this is NOT the only known way to protect pig kidney tissue from the complement and/or coagulation-mediated destruction caused by the primate immune response. The other known way of protecting pig kidney tissue via genetic manipulation is to insert human transgenes that can protect against human complement, coagulation, or inflammatory responses (Wijkstrom et al, 2017).
The expression of a human complement-regulatory protein like CD46, CD55, or CD59, and/or a human coagulation-regulatory protein like thrombomodulin, tissue factor pathway inhibitor, or endothelial protein C receptor, has been shown to provide graft protection. Further graft protection is made possible by the ‘knockout’ of the following pig antigens: galactose-α1,3-galactose, N-glycolylneuraminic acid, and the Sd(a) antigen. A substantial reduction of primate antibody binding to pig vascular endothelial cells has been identified in the absence of the expression of these pig antigens. All of the aforementioned genetic manipulations have resulted in a decrease in antibody-mediated rejection after a pig organ has been transplanted into a non-human primate. (Wijkstrom et al, 2017)
Priya: Wow! Ok - leave it to our intricate complement pathway, to again, play such a pivotal role in our immune system. I mentioned the knockout pigs earlier in the show, so I’m glad that you took the time to explain the importance of it now. We really couldn’t have moved forward in this research without the isolation of those specific antigens and getting rid of them. Ok, so if that was the lie, why dont you tell us more about the rest of the statements. Lots of interesting stuff to say I would think.
Christel: Statement 2 Explanation: Moving on to our second statement, it is absolutely true that in the early studies of pig kidney xenotransplantation, moderate-to-severe proteinuria with resulting hypoalbuminemia were uniformly documented, which required frequent infusion of human albumin. (Soin et al, 2001). It was uncertain as to whether these findings were due to activation of the immune response or to some sort of inherent physiological incompatibility between pigs and primates. However, in more recent studies involving non-human primates transplanted with pig kidney grafts, there has been minimal proteinuria with an absence of hypoalbuminemia noted (Iwase et al, 2015). This strengthens the argument that activation of the immune response was a more likely cause of the earlier findings of proteinuria as opposed to physiological incompatibilities, especially in the setting of better control of the immune response due to the genetic modifications of donor pigs and/or immunosuppressive therapies (Iwase et al, 2015; Wijkstrom et al, 2017).
Priya: Its great to hear that the proteinuria seems to be more under control, and again, it seems to be all linked to the fact that we are using knockout pigs for transplant. Proteinuria can be such a non-specific finding...with so many conditions causing it. And in transplant, sometimes it might be the first and only sign of problems that may come down the road for the graft. So, knowing that you will likely have minimal proteinuria in our early studies of xenografts is great know - so that in the future we can look at other potential causes and rule out species physiology mismatch sooner. Ok, how about we move on to your last truth?
Christel: Statement 3 Explanation: For sure! Last but not least, it is true that the FDA has suggested that xenotransplantation be limited to “patients with serious or life-threatening diseases for whom adequate safe and effective alternative therapies are not available”, while limiting the therapy to those patients “who have potential for a clinically significant improvement with increased quality of life following the procedure” (Wijkstrom et al, 2017). Populations that are thought to be included in this recommendation include those who have had a high degree of allosensitization to human leukocyte antigens, and/or rapid recurrence of primary disease in previous allografts (Wijkstrom et al, 2017). Populations precluded from renal xenotransplantation as a result of this recommendation include those in which allotransplantation is contraindicated due to chronic infection or malignancy, for these would likely be associated with very poor outcomes due to the degree of immunosuppressive therapy needed to keep the transplanted kidney healthy (Cooper et al, 2017; Wijkstrom et al, 2017). This recommendation from the FDA is critical, because it provides additional guidance on who should be included in a pilot clinical trial of pig kidney xenotransplantation (Cooper et al, 2017).
Priya: Wow that was really insightful, thank you for that interesting information Dr. Wekon-Kemeni! I’m sure we all learned a thing or two (or three!) from your statements. Now let’s move on to Dr. Mo. Why don't you go ahead and share our last set of truths and a lie!
Mo:
Thank you Priya
Now these are my statements for the audience to try to figure out which ones are truth and which are lies!
Xenotransplantation could result in the transmission of organisms that may not normally be pathogenic in humans but can become so in the immunocompromised individual
Religious authorities completely oppose all forms of xenotransplantation.
Non-human primates are no longer considered for future use in xenotransplantation.
Priya: Ok, lots of things to address here. First, infection, which again, is huge in the transplant world. Then, we have society’s thoughts on such a hot button topic, for which we could do an entire podcast episode on just that. And then the potential use of different species outside of pigs. I dont even know where to start, so I’m just gonna ask Zac. Zac, what are your thoughts about these statements?
Zac: Hmm, this is a tough one! Well, for statement 1, we talked about PERVs a little bit earlier, and established that those have not been shown to infect the xenotransplant recipient, so maybe that statement is a lie? I would imagine that there are some other conditions out there that could be transmitted, especially in the context of immunosuppression, so I could see this going either way. For statement 2, there are definitely some important ethical and religious considerations surrounding xenotransplantation. I know some religions have strong beliefs surrounding particular animals and their consumption such as Kosher in Judaism and Halal in Islam. I could definitely see there being some religions that frown upon xenotransplantation, at least from particular animals, but it seems a bit strong that they would outlaw xenotransplantation entirely. For the third statement, non-human primates certainly should be a closer match to humans, and I would imagine they must be more compatible for xenotransplantation, but I’m certainly no expert in the field! Ultimately, I think I’m gonna have to guess that statement 3 is the lie!
Priya: Ok, yea - I definitely like how you walked me through that…because there was a lot to unpack with each of these statements. And sometimes, I get lost in my own head. Christel, what are your thoughts?
Christel: This is tough, but my gut (and test-taking skills) are telling me that statement #2 is the lie. It seems like a vague and absolutist statement, and it makes more sense to me that the other two statements would be true.
Priya: Of course, you can never go wrong with using all of the test-taking skills we have learned over the years! So, I think that I would agree with you, Christel, and think that statement two is a lie. So, Mo - what is the final verdict? Take us through your statements.
Mo: So, for the first statement: Xenotransplantation could result in the transmission of organisms that may not normally be pathogenic in humans but can become so in the immunocompromised individual; this is a true statement. And this is mainly because it is difficult to predict the pathogens that may cause infection in a recipient of a xenotransplanted organ only on the basis of our knowledge of naturally occurring zoonoses. This is because there are big differences between normal contact of humans with animals and contact of a recipient with a xenotransplanted organ. For example, the distance barrier is eliminated in the recipient, due to the vascularization of xenotransplants, or even implantation of non-vascularized tissues during the procedure. The potential for viral adaptation in immunocompromised recipients and the potential for undetected spread of latent viral infections are concerning. For these reasons, during xenotransplant trials, close monitoring of infectious pathogens in the recipient is very important, however it is equally important to consider the safety of their contacts and also the public. (Fishman, 2018)
Priya: Thanks Mo. Again - infection is always going to be a topic on the tip of our tongues when it comes to anything in the transplant world. So, while I was, of course, hoping that this was a lie, I am not surprised that it isn’t. I know that with these knockout pigs, we are able to focus in and remove particular molecular markers in the setting of immunity, but I wonder what other CRISP technology can be used to target innate organisms in the porcine microbiome that may not agree with humans. Technology has come so far, so I can’t wait to see how it affects transplant ID. Ok, so we haven’t found our lie yet, whats your next statement?
Mo: Now for the second statement: Religious authorities completely oppose xenotransplantation. Despite being widely controversial, this is actually not true. The origin of this is that some religions like Judaism and Islam forbid consuming pig meat. So, the general population of these religions tend to consider that xenotransplantation of pig organs into humans has the same ruling. Even some Christians raised ethical concerns about xenotransplantation. However, despite the general belief, the majority of the religious authorities of these religions did not oppose xenotransplantation. In 1999, a bio-ethicist from Queens Hospital “Dr. Fred Rosner” has published an article (Rosner, 1999), which has explored the Jewish view of using pigs for xenotransplantation, He concluded that although Jewish law forbids Jews to raise or eat pigs, no such rule for the use of pigs to cure human illness or to save human lives by xenotransplantation. By the same token, in the year 2000, The head of the Catholic church Pope Paul John II, stated the Vatican's acceptance of the transfer of animal organs to humans, as long as the result does not harm the recipient physically or psychologically. Most recently, in October, 2021, following the NYU kidney xenotransplant case. Egypt's top religious institution, Al-Azhar, which Muslims around the world look to for guidance, has ended an ongoing debate by issuing a religious ruling (The New Arab, 2021) permitting pig's kidneys to be transplanted into a human body if no other alternatives are available to save the patient’s life.
Priya: I’m really glad that you brought this up Mo, because in the medical world, I know many of us are excited about xenotransplantation. We are in a time where our population has many people at...or near end organ failure. You and I, just happen to be in the world of transplant nephrology, and we see so many patients on dialysis, waiting for a transplant. So, we see xenotransplant as this amazing opportunity: to help patients to get off dialysis. And in the case of the Maryland group, other organs, such as heart transplant. But, other people outside of our medical world might see the idea of transplanting from pigs differently. I’m happy to see that more people are open to the idea than against it, but this may be a point of contention that will always linger in the background. Ok moving on - so, our last statement is true then? Tell us more about that.
Mo: And finally, for my third statement: Non-human primates are no longer considered for future use in xenotransplantation. Actually, this is a true statement. Non-human primates trials involving kidneys, hearts, and livers were conducted in the 1920s to 1990s, as they were genetically closer to humans than pigs. However, researchers found that there were several limitations that made them not suitable, including ethical concerns, high risk of cross-species infection transmission to humans, difficulties in breeding, and organ size differences, just to name a few. It was not until 2003, when genetically modified knockout pigs were available as the source for xenotransplants, and they have several distinct advantages. Pigs are easier to raise, grow up quickly, and will have organs similar in size to a human adult within a 6 months period. Pigs also reach reproductive maturity quicker for large mammals. They also have relatively large litter sizes, and have physiologic and anatomic similarity to humans.
It is for these reasons, that since the 1990s, porcine xenotransplants have overtaken non-human primates as the future of xenotransplantation. Of course, there is still the obvious genetic discrepancy that results in immunologic rejection and porcine infections as was discussed earlier by my colleagues (Lu, 2020, Carrier, 2022)
Priya: Okay! Thanks Mo! Finishing our episode strong. So I guess the humble pig comes out on top ... as our xenograft species of choice! I never realized that these genetically modified knockout pigs have been available for almost 20 years now! You know, its funny. I look back at my time - while prepping for this episode - and how I originally thought that this was up and coming research, but its easy to forget how long and hard people have been working - all the benchwork and basic science research that happens before it reaches the bedside. More and more research is going to pop up, because others are currently working on projects that we don’t even know about. I know there are other ideas being explored, like tolerance-inducing strategies, such as simultaneous thymic transplantation, which, in theory, may allow for the reduction or cessation of immunosuppressive medication, which is very exciting to think about. I know we have a long road ahead in the field of xenotransplantation, but these lines of research and other future topics will start to surface and come to light as the years go by. Anyways, you can’t help but agree…this is a very exciting time to be in nephrology.
Well everyone, that ends our show for today: 2 truths and lie: Renal xenotransplantation edition. A special thank you to our panelists: Zac, Christel, and Mo. It was such a pleasure to chat with you guys on such a cool topic. I also want to thank all of you for joining us in our conversation regarding such a hopeful field. I know that I learned quite a bit about the topic from my colleagues and I hope you did too. Be sure to tune in to our next episode where we discuss another thought provoking topic…and what lies ahead in our ever-changing field that is nephrology. Thanks again for joining us, my name is Priya. See yall next time!
