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[00:00]
A
Hey there. I'm Rachel Feldman and I host a podcast from Popular Science called the Weirdest Thing I Learned this Week. Every other week, I circle up with guests like Bill Nye, Josh Gondelman, Mary Roach, and many more to prove that the lofty and noble pursuit of science can also be profoundly weird. From flying Ford Pintos to the world's most illegal cheese, the weirdest Thing I Learned this week is the ultimate source for all things interesting, informative, and, and most importantly, frickin weird. Check out the weirdest Thing I Learned this week. Wherever you get your podcast, come on over whenever you're ready to get weird.
[00:35]
B
We're talking about trying to retrain the immune system so we don't have to just reduce the immune responses to anything, but just trying to reduce the immune responses to the organ itself so that we can re educate the immune system and mitigate the side effects that the immunosuppression drugs come with.
[00:52]
A
A donated organ can save your life, but from the moment it's placed inside your body, your immune system sees it as an invader and tries to destroy it. For decades, the solution has been powerful anti rejection drugs. But what if there's a new way? If we could teach the immune system to make peace with a transplanted organ instead of fighting it? That idea once seemed impossible, but now scientists are looking to the body's own own playbook, unlocking the liver's unique ability to promote immune tolerance and developing therapies designed to teach the immune system acceptance rather than suppression. That's what we're talking about on this episode of Tomorrow's Cure from Mayo Clinic, a podcast that brings the future of medicine to the present. Lindsey, I'm Lindsay Sievert. It's great to have you with us. Joining me are Dr. Timotin Tanner, a transplant surgeon at Mayo Clinic, and Dr. Angus Thompson, a transplant immunologist at the University of Pittsburgh Medical Center. Dr. Tanner and Dr. Thompson, it's so wonderful to have you both here for this conversation today. And before we get started, I heard you talking earlier and I understand that you're longtime colleagues. Tell me a little bit more about your capacity of which you've worked with one another.
[02:11]
B
Yeah, thank you very much, Lindsey. It's an honor to be here. We go back quite a while. Angus was my PhD advisor and mentor and has been my mentor ever since. I owe him a lot to what I became today.
[02:24]
C
For me, it's been extremely gratifying to see Dr. Tanner flourish in his career, becoming a leading, internationally recognized surgeon scientist who contributes continually to or organ transplantation. It's always been a great pleasure to have been his early mentor and to remain friends for many years.
[02:47]
A
Well, that is just wonderful. And before we get into this conversation, I'd just love to set the stage, since you both specialize in transplant medicine and started all those years ago. So for listeners, when they think about transplant medicine, many might just think about just the surgery itself. Many don't know that transplantation is really the beginning of a long relationship between a patient, a new organ and the immune system. And for more than 50 years, transplant medicine has relied on this trade off. You get a new organ in exchange for a lifetime of medication. But researchers are chasing what many call the holy grail of transplantation, A future where some patients may no longer need anti rejection drugs at all. So that's what we're diving into in this episode. And Dr. Tanner, can you just give us a short summary of the reason why we're talking today?
[03:37]
B
We're talking about trying to retrain the immune system so we don't have to just reduce the immunos the immune responses to anything, but just trying to reduce the immune responses to the organ itself.
[03:49]
A
Dr. Thompson, how would you give us your elevator pitch of that same advance?
[03:55]
C
As Dr. Tanner has said, we are currently highly dependent on anti rejection drugs that are nonspecific in how they affect the immune system. It's rather like a blanket suppression of responses to all foreign entities. Where the field is going is towards selective suppression of the anti donor response. And these approaches show significant promise in being able to instill unresponsiveness specifically to the donor, which would be of great benefit to the patients in reducing their dependence on non specific immune suppression and eventually becoming independent of these anti rejection medications.
[04:54]
A
While advances in medicine explore these different kinds of cell therapies, they all share the same teaching the immune system how to accept a transplanted organ. That way, patients may someday rely less on lifelong anti rejection medication.
[05:10]
B
Just to give you a scope of the issue, in the United States, about 50,000 people get an organ transplant every year. So if you add this up, it adds up to 500,000 people in 10 years. In the world, we're approaching 180,000 transplants a year. So this is the scope of the problem. This is a problem that the modern medicine created. Transplant was not available 50 years ago. Now it's readily available. It's one of the most successful treatments that we can offer.
[05:43]
A
So Dr. Tanner, at what point do immunosuppression drugs come into the picture and can you help us understand why they are such a central part of transplant care?
[05:52]
B
Immunosuppression drugs come in to the field right away, at the time of the transplant because the immune system works in a way that it's designed or evolved to react to anything that's not a self. Any different organ coming from a donor in a recipient's body will be seen as a foreign. It's got to have a lot of proteins that are seen as a foreign. So the immune system starts recognizing it within minutes and starts attacking it. So the immunosuppression medications are there to, to suppress that response, to modify it so that the organ does not have a rejection. If you don't control, this is what we call the rejection.
[06:36]
A
And that is a reality for many patients that do experience rejection or they, they can correct.
[06:42]
B
So unless the immune system is adequately suppressed, people will have rejection. Rejection may sound like a scary word, but once detected and treated adequately, it usually does not lead to long term consequences. But it needs to be treated with most of the time enhancing immunosuppression, increasing the dosage of the immunosuppressant medications.
[07:06]
A
And what does that look like for, let's just say a liver transplant recipient? Is it a daily pill? What kind of, what is, what kind of medication is it?
[07:14]
B
So let's say a liver transplant recipient, they start with a regimen of three different immunosuppressant drugs. They are all pills. They take this every day. And usually because of the liver's unique tolerogenic ability, we're able to reduce that to just one drug, one at night, one in, in the morning, after the first few months. But we don't have that luxury in other organ transplants. Most other organ transplants, including kidneys, lungs or hearts, people may need to continue taking two or three different medications throughout their life.
[07:52]
A
And these medications can have some tough side effects in some cases.
[07:56]
B
Correct. These drugs, as effective as they are, unfortunately come with some side effects. Correct. People may have increased incidence of infections, increased incidence of some certain types of cancers, and they also increase the incidences of diseases like diabetes and hypertension.
[08:15]
A
So let's say that someone receives a new organ. At what point do those anti rejection drugs come in? Is it immediately?
[08:21]
B
It starts immediately whenever we use an organ for somebody else. The organs, we all have different genetic makeup, so we all have proteins on our organs that are seen as a foreign by the recipient's immune system. So you have to train the immune system not to see that protein as a foreign antigen. So you have to start that at the very beginning, right at the time of the transplantation.
[08:49]
A
Dr. Thompson, we've all heard the stories of people waiting for an organ for so long. What do people misunderstand about anti rejection medicines?
[08:58]
C
It's important for people to recognize just how much enormous progress has been made, certainly in my lifetime from considering transplantation as something that really was not possible, to something that has become relatively straightforward standard of care procedure. I think people do appreciate that immunosuppressive drugs are effective. They do recognize that there are certain untoward effects that can accumulate over time. It's remarkable that we are dependent on the same armamentarium of drugs that we've been using for the past two to three decades or even longer. And that advances towards the holy grail of being able to minimize discontinue anti rejection drugs over time has proven a really tough challenge. Although many advances continue to be made that give us a great deal of hope that we will in the foreseeable future be able to get larger numbers of patients on very low doses of anti rejection therapy and even awful immunosuppression altogether.
[10:18]
A
What is the Holy Grail? I heard you say something. The idea that someday a patient will receive a transplanted organ without being on lifelong immunosuppression medicine. Is that what that is?
[10:29]
C
Well, yes. The Holy Grail was a term that was coined many years ago by immunologists and surgeons. And it's the vision that a state of transplantation tolerance can be achieved in patients. And by tolerance, the patient is able, at some stage post transplant, usually many years, to become a potential candidate for withdrawal of all immunosuppression. This is possible in liver transplantation where depending on length of time post transplant, it may be possible to cautiously withdraw immunosuppression from the patient and the patient does not reject. But that has not, as I mentioned earlier, been an easy thing to prospectively undertake.
[11:22]
A
Dr. Tanner, that holy Grail. The best chance of studying that holy grail or getting closer is, I heard Dr. Thompson say, is within the liver. So what work is underway at Mayo Clinic where you're studying this closer?
[11:36]
B
Yeah. So before that, let me tell you why the liver we think is special. Because liver is, through the evolution, just trained itself to not react to these proteins, these antigens, because it's constantly exposed to dietary antigens. So whenever we eat or intake something, it goes through the bowel and it gets absorbed and all that nutrients, they get into the bloodstream and that that blood goes through the liver. So liver is trained to see those antigens and not react to it. So it's just one of those evolutionary things that allowed us to come this far. Because of that, through many years of research, we know that the liver transplant recipients, just as Dr. Thompson said, are probably the first cohort of transplant recipients that we can try to achieve tolerance in. We have done several trials trying to get or induced tolerance in liver patients. And Dr. Thompson has done a very innovative trial at his place using those. The trials we have done at Mayo Clinic are those that involve infusion of cells into the recipient called regulatory T cells. So these are lymphocytes, or white blood cells that are in charge of controlling their counterparts. So they are the gatekeepers, so they control the other lymphocytes from attacking the liver.
[13:01]
A
As researchers at Mayo Clinic and the University of Pittsburgh test new approaches, they work towards the same goal. Retraining the immune system so transplant recipients could one day face fewer side effects and a better quality of life. Has this been a problem that you've been trying to solve as clinicians since you all the way since you worked in Dr. Thompson's lab?
[13:22]
B
I completely agree with Dr. Thompson's sentiments about the immunosuppression drugs and how it made us this successful. We recently had a 50 year celebration of our abdominal transplant surgery division and looking back, it gave us a chance to reflect on the progress we made in 1975 and kidney transplant recipients had about 30% of expected one year survival and we are now talking about over 99% thanks to these anti rejection medications. However, they do come with certain risks. Recently, the American transplant society did a survey in over 10,000 transplant recipients. And 92%, while they were very grateful and happy with their progress, stated that they had at least one side effect of these anti rejection medications.
[14:13]
A
So Dr. Thompson, tell me what's underway at your lab with this research?
[14:18]
C
For many years. This goes Back to when Dr. Tanner was doing research in Pittsburgh and earlier. We've been interested in a particular type of immune cell actually different from the regulatory T. T. Cells that Dr. Tanner has described. The cells that we are focused on are not lymphocytes, but innate immune cells of the myeloid, not the lymphoid system. And these cells have the ability to to very effectively regulate immune responses. So in the trials that we have been conducting in live donor liver transplantation, we generate these regulatory cells from the prospective liver donor and we infuse the cells before transplant or after transplant into the liver recipient. We follow the patients for a year, we perform what is called a protocol biopsy one year post transplant and if the patient is clinically stable and has no evidence of any ongoing rejection, we can cautiously begin to withdraw immunosuppression. And in some patients we have been able to withdraw immunosuppression completely. And then in following these patients, they have remained off all immunosuppression for three or more years post transplant. So we are encouraged by, first of all, the feasibility of doing the study, the safety of the cells when infused into the patient, and what we would call exploration of efficacy. We have some encouraging signs that this intervention may be successful. However, we have to now undertake what's called a randomized trial to formally test efficacy of the cell therapy approach to improving outcomes.
[16:25]
A
When researchers take specialized immune cells from the organ donor and give them to the transplant recipient before or after surgery, again, the hope is that these cells help recognize the new organ as something it doesn't need to attack. The science is still evolving, but the promise is significant. Researchers are now working to confirm those results in larger clinical trials.
[16:54]
C
Busy Healthcare Professionals this one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit ce mayo.edu podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by male clinic experts.
[17:32]
A
What is the breakthrough that allows some of the successful patients to withdraw from their immunosuppression drugs altogether?
[17:39]
C
These donor derived cells express the crucial donor antigens that are recognized by the recipient before transplant. And we believe that the cells bearing those donor antigens that also have an immune regulatory function teach the recipient's immune cells to be less responsive to the donor organ when it's transplanted into the body.
[18:10]
A
Dr. Tanner, what is the breakthrough here for you and your work?
[18:14]
B
This all shows me that we're getting one step closer every time we talk about this. There are several approaches. Dr. Thompson's approach has been very successful at Mayo. We are also trying to retrain the immune system of the recipients. Another way of doing this is trying to achieve what's called a chimerism. So if you can retrain the immune system by introducing the donor's immune cells into the recipient and they start to live together without attacking each other, then you can put that donor's organ into the recipient without having to worry about rejection because you had already retrained it. So that is done through infusion of stem cells that are obtained from the recipient. All these kind of approaches, including the regulatory T cell approaches, Are just taking us one step closer to achieving or getting to that holy grail that we've been talking about.
[19:07]
A
What was the term that you called it? Kind of teaching the cells?
[19:11]
B
Yeah, retraining the immune system is what I call it. It is really trying to retrain the immune system, because immune system evolves to fight against anything foreign to us. That's how we can survive infections. That's how we survive cancers, because what is not ours is foreign and we have to fight it. That's how the immune system works. If we can retrain it not to react to just specific proteins that are on the surface of that organ without changing its reactivity to infections or cancers, that would be the tolerance.
[19:46]
A
If we could look through a microscope, what happens when you introduce some of these donor cells to the recipient and they teach the other cells? How does that work?
[19:57]
C
Perhaps I can address that. Because our studies are specifically focused on infusing donor derived cells in the context of living donor liver transplantation. We believe that these cells, when they are infused into the body, actually don't survive very long, but they pass on messages to the recipient immune system. And these messages are, we believe, conveyed in the form of small particles, or vesicles, that are derived from the infused donor cells. And these particles, they're sometimes called small vesicles, extracellular vesicles, they convey the donor antigen, but in addition, they also convey instructions, protein molecules, and possibly also RNA molecules, that, when they are accepted by the recipient immune cells, condition those recipient immune cells to be unresponsive specifically to donor antigen, because the donor cells that were infused express the donor antigen. And studies that we've done for many years at the university of Pittsburgh do indicate that this is how the cells are instructing the host immune system to be less responsive or unresponsive to the donor organ.
[21:31]
A
When all this happens, when all these messages are received, what does the liver then do next? Or how is the liver sort of a clue that this is effective?
[21:40]
B
Yeah, liver has a way of retraining the immune system itself, but we have done several studies here at mayo clinic Showing that the liver itself, after the transplant, Changes the immune responses against it through working with the recipient immune system. That's how it tends to protect the simultaneously transplanted organs from rejection. When you do a liver and a kidney transplant, the incidences of rejection in the kidney are just much, much lower, despite the same immunosuppression. So we know that liver has that capacity, achieving that, as Dr. Thompson said, would allow us to just reduce the immunosuppression very controllably, slowly making sure there's no injury to the liver and eventually to completely get rid of the immunosuppression that people have to rely on. I think each of us are making progress through our own unique ways, trying to retrain the immune system. As I said at Mayo Clinic, we have several upcoming trials in liver transplant patients. But in addition to that, something we haven't talked about, we have started aiming at other organ transplants as well as. Just because liver seems to be a little easier should not lead to just working on liver transplant patients because everybody else also needs this kind of innovative approach. So we have infused cells into the kidneys of kidney transplant recipients with rejection to slow down the rejection, using or mimicking the biology, using some of the anti inflammatory cells to help us reduce the inflammation within that. Those have been successful thus far. As Bell and just like Dr. Thompson said, we are at the face of expanding those trials to do more efficacy studies.
[23:29]
A
Dr. Thompson, what is the potential, as Dr. Tanner just mentioned, of other organs, he mentioned kidney. What other organs could this be effective with? Or what are you studying there?
[23:40]
C
I think we have to recognize that while the spontaneous occurrence of transplantation tolerance is relatively common in liver transplantation, it is very rare, exceptionally rare in kidney transplantation, but it does occur. So these natural occurrences of transplant, clinical transplantation tolerance really encourage us to pursue the cutting edge approaches that we believe a step at a time will take us closer to the holy grail of transplantation tolerance. So kidney is clearly amenable to many of these innovative approaches to conditioning the organ or conditioning the recipient with innovative therapeutic agents, whether it's cell therapy, body biologics, new biologics or new pharmacological agents, the heart and lung where perhaps the greatest unmet need these organs. Clearly the patients would benefit from the same advances. And although it is more challenging, it is still possible to think about applying these approaches and thoracic organ transplantation.
[25:05]
B
Thoracic organ transplants, heart and lungs are life saving transplants. Day two need to be on anti rejection medications because the consequences of having a rejection in those organs are quite high. Then they are kept on higher doses of immunosuppression. So it would be great to be able to take these innovative approaches to the thoracic organs, as Dr. Thompson said. And I'm hopeful that we're getting closer and closer to that point.
[25:34]
A
I love what you said, that transplant medicine has become so refined and sophisticated over the past 50 years that in solving one problem we've created another. And now it's your moral imperative really to solve this other problem with immunosuppression medicine. Is that how you see it, Dr. Thompson? This is the new frontier for you as an immunologist?
[25:56]
C
Yes, as an immunologist, my career long goal has been to ultimately improve outcomes for the transplant patient, reduce dependency on anti rejection therapy and getting closer to the goal of clinical transplantation tolerance. We have a recurring very real issue of inadequate supply of donor organs.
[26:22]
B
That's a real issue and that has been a real issue ever since transplant has started. We simply do not have enough organs for people who are in need of organs. So a lot of progress on that has been made also. Part of that is thanks to the advances made in immunology as we've been talking about. And part of that is trying to find other sources of organs like xenotransplantation. Genetically modifying non human animals with similar sizes to humans to make them more suitable for transplantation. There's been a lot of progress in that in the last few years too. There are a lot of immunological issues that goes with that. But most of those issues have been tackled now compared to where we were 20 years ago. And that is becoming a reality in the next few years as well.
[27:14]
A
So xenotransplantation. So that's organs that are sort of modified from animals like you said, like pig.
[27:22]
C
Correct.
[27:22]
B
The most common source is pigs because pigs have very similar sizes of their organs as humans. So that makes sense. And genetically modifying these pigs to make them more similar to the human organs. The initial trials are on their way to start from probably with kidney and heart transplants. You might have heard or read the news about those things. Larger trials are coming in several centers, including Mayo Clinic, that will involve trying these organs in patients who are in desperate need of organ transplantation.
[27:57]
A
I'd love to bring it back to the patient. I hear a lot of excitement in where this is headed, but also a lot of careful optimism that you have to go, you have to take the next step and the next step. What have we learned so far from the patient journey? I know that there are still many patients out there trying to stop medications after years of what's known as tolerance focused therapy.
[28:18]
C
The willingness of patients to participate in promising clinical trials is very precious. And as clinicians and scientists, we are very grateful to patients and their families for participating in in these studies that offer, as Dr. Tanneha said, considerable grounds for optimism. And as transplant scientists, we, I feel, are entitled to be optimistic because of the incredible strides that have been made. And I think that inspires us, it inspires patients, and it inspires families to have optimism about the future of the field.
[29:01]
A
A lot of short daily news podcasts focus on just one story, but right now you probably need more on up first from NPR. We bring you three of the world's top headlines every day in under 15 minutes, because no one story can capture all that's happening in this big crazy world of ours on any given morning. Listen now to the up first podcast from NPR. Dr. Tanner, what what do you hear from patients that have received organ donations and what do they face?
[29:31]
B
Transplant recipients are very grateful to their donors. The first thing is that we cannot do any of this without the donor. So a lot of credit goes to donors, whether they are deceased donors or living donors. That is truly a gift of life. So that's number one. Number two, most recipients really are very proud of the process they went through to get a transplant, and they want to keep that transplant as long as it goes forever. And that's our goal as well. So our job is to help them do that. So all these efforts to try to reduce the immunosuppression, to get them off the immunosuppression is to help them get to that healthy life and keep that precious gift as long as possible.
[30:12]
A
Dr. Thompson, there is another link between what we're talking about today with transplant tolerance research, but also autoimmune conditions like diabetes, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis. So I'd love to hear how you're learning. What you're learning now can also have a lot of potential with autoimmune disease treatment as well.
[30:35]
C
Those of us who perform science and transplantation and perform science in the many autoimmune diseases share an understanding of mechanisms that prevail in both conditions. The immune response is an undesired phenomenon in transplantation and in autoimmune diseases. And the two fields do learn and are instructed for one another. The development of immunosuppressive drugs in the field of transplantation led to their application in numerous autoimmune disorders. And similarly, the successful trials of immunosuppressive agents in the field of autoimmunity can be instructive for transplantation. There have been quite a number of examples of this two way relationship. One field learns from the other reagents that may prove new agents that may prove to be very Effective in controlling certain autoimmune disorders, may be valuable for testing in organ transplantation, that overall there are many mechanisms that are similar between the rejection of an organ transplant and an immune mediated autoimmune disorder.
[32:05]
B
Yes, I completely agree with all that. So immune system plays a major role in a lot of disease processes. So while transplant is allowing us to study this in a sort of a man made disease condition, the findings are helping other patients like those with autoimmune disorders.
[32:24]
A
I'm just curious, when you look decades into the future, what research implications are there beyond today's transplant patients? I'm thinking about lab grown organs, gene edited organs, or other technologies that we're just beginning to explore.
[32:39]
B
Those are all on the table and a lot of people are working on different parts of this whole progress. In the future we should be able to grow organs or parts of the organs in the lab. We should be able to adequately modify the genetics of animals or lab animals that we can take their organs from and transplant into people. Hopefully the field will look much different in the next 30, 40 years as it looks different now compared to 30, 40 years ago. I think the progress has been very exciting in this field.
[33:13]
A
Dr. Thompson.
[33:14]
C
Yeah.
[33:15]
A
If these advances continue to move forward, what does this mean for patients and families living with the realities of transplant today? And what do you hope for? What do you imagine?
[33:25]
C
I think these advances instill enhanced optimism about continued progress. There's a remarkable shared vision between clinicians, scientists and donors, graft recipients and their families. And this shared vision is something that I personally feel really does help sustain the field. So if we think a generation ahead, I believe we will be less dependent on the conventional anti rejection drugs that we've been dependent on for so many years. And we will be using approaches that have less side effects, cumulative side effects over time.
[34:14]
A
Thank you so much. And Dr. Tanner, as Dr. Thompson was speaking, I was thinking just what promise or what hope is on the horizon as a gift to your patients who have really been through so much, to be able to tell them there is something around the corner has got to keep you hopeful as well.
[34:33]
B
If you take a step back and look at the transplant process, you realize that how much progress has been made over the past 50 years or so, I would tell the patients that the progress is going to continue. Thanks to the donors, we're able to do all these studies, adding scientific data to their care and this is all ending up with better and better graft survival, better patient survival, and we're very optimistic about the future in transplant Medicine.
[35:03]
A
In our podcast, Tomorrow's Cure, we really focus not only on innovation, but that that grounded sense of hope. And I'm just wondering where you're at with your studies and your research. What gives you hope and maybe a little bit of wonder about the future of transplantation?
[35:17]
C
I think that the history, the developments, and the shared optimism about the future are what will continue to drive this field forward.
[35:28]
A
Yeah, Dr. Tanner, it really is this ecosystem of care all the way from the person who decides to give their organ all the way to this moment.
[35:37]
B
This all goes back to transplanting being really a team sport. There are some things in medicine that involves just the patient and the treating physician. Transplant is not one of them. Transplant is a unique treatment in medicine that involves two individuals, really connects two individuals. The donor and recipient comes with a whole team that supports the success of that transplantation and that unites the team, including clinicians, the basic scientists. That gives us hope that this will continue to improve and the outcomes will be much better than what they are now, which is still fantastic.
[36:17]
A
Wonderful. Well, thank you both so much for your history of collaboration, for your research, and for enlightening us today. I really also approach this field with hope for all the patients who have been through so much. So thank you. Thank you again.
[36:32]
B
Thank you very much, Ninzi.
[36:33]
C
Thank you. It's been a privilege.
[36:36]
A
Tomorrow's Cure is a production of Mayo Clinic with production help from the Podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts. And if you liked today's episode, please like and subscribe. I'm Lindsay Siebert. Thank you so much for being with us.

Summary6 min read

Podcast Summary:

Tomorrow’s Cure – How Scientists Hope to Retrain the Immune System After Organ Transplant
Host: Mayo Clinic (Lindsey Sievert)
Guests: Dr. Timotin Tanner (Transplant Surgeon, Mayo Clinic), Dr. Angus Thompson (Transplant Immunologist, University of Pittsburgh Medical Center)
Date: August 5, 2026

Main Theme

This episode explores the evolving frontier of organ transplantation: training the immune system to accept donor organs without life-long reliance on broad immunosuppressive drugs. The conversation dives deep into new approaches aiming to induce specific immune tolerance toward transplanted organs, especially utilizing the liver’s unique properties. Experts from Mayo Clinic and the University of Pittsburgh discuss promising advances, patient impact, and the future of transplant medicine.

Key Discussion Points & Insights

1. The Challenge of Transplant Rejection and Immunosuppression

Traditional Approach: For decades, organ transplant recipients relied on strong, non-specific immunosuppressive drugs to prevent organ rejection.
- "A donated organ can save your life, but from the moment it's placed inside your body, your immune system sees it as an invader and tries to destroy it... But what if there's a new way?" — Lindsey (00:52)
Trade-Offs: These drugs prevent rejection but expose patients to infections, cancers, diabetes, hypertension, and other side effects.
- "These drugs, as effective as they are, unfortunately come with some side effects." — Dr. Tanner (07:55)

2. Toward "The Holy Grail": Immune Tolerance

Vision: The ultimate aim is transplant tolerance: patients eventually don’t need lifelong immunosuppression.
- "The holy grail... is the vision that a state of transplantation tolerance can be achieved in patients." — Dr. Thompson (10:28)
The Liver’s Special Role: The liver’s evolutionary adaptation to continual antigen exposure makes it uniquely tolerant, providing a model for studying immune acceptance.
- "Because the liver is constantly exposed to dietary antigens... it's trained to not react. That allows us to try tolerance in liver transplant recipients first." — Dr. Tanner (11:35)

3. Cutting-Edge Approaches: Cell-Based Therapies

Regulatory T Cells (Tregs): Infusing recipient with donor-derived regulatory T cells can prevent overactive immune attack.
Myeloid Regulatory Cells: Dr. Thompson’s team focuses on another type of regulatory cell from donors (myeloid, not lymphoid cells) infused around surgery time.
- "We generate these regulatory cells from the prospective liver donor and we infuse the cells before or after transplant into the liver recipient... In some patients, we have been able to withdraw immunosuppression completely." — Dr. Thompson (14:17)

4. Mechanisms of Retraining the Immune System

Chimerism: Introducing donor immune cells into the recipient to help the immune systems coexist peacefully.
- "If you can retrain the immune system by introducing the donor's immune cells... then you can put that donor's organ... without having to worry about rejection." — Dr. Tanner (18:14)
Cellular 'Messaging': Donor cells may not last long but release vesicles (tiny packages) containing proteins, antigens, and messages that 'teach' recipient cells tolerance.
- "These particles... convey the donor antigen, but also convey instructions... when accepted by the recipient immune cells, condition those cells to be unresponsive to donor antigen." — Dr. Thompson (19:57)

5. Extending Innovation to Other Organs

Beyond Liver: Progress is most advanced for livers, but similar principles are being explored for kidneys, hearts, and lungs.
- "Kidney is clearly amenable... the heart and lung, where perhaps the greatest unmet need [is]... although it is more challenging." — Dr. Thompson (23:39)
- "We have started aiming at other organ transplants... we've infused cells into the kidneys... to slow down rejection." — Dr. Tanner (21:39)

6. Future Directions: Organ Shortage & Xenotransplantation

Organ Supply Problem: There are still not enough donor organs, leading to exploration of genetically engineered animal organs (xenotransplantation), especially from pigs.
- "Genetically modifying these pigs to make them more similar to human organs... initial trials are on their way." — Dr. Tanner (27:22)

7. Patient Perspective and Collaboration

Patient Journey: Transplant recipients are deeply grateful, want to make the most of their organ, and are often eager to participate in research to help others.
- "The willingness of patients to participate in promising clinical trials is very precious... as clinicians and scientists, we are very grateful to patients and their families." — Dr. Thompson (28:18)
Team Effort: Transplant success is credited to collaboration among donors, recipients, clinicians, and researchers.
- "Transplanting [is] really a team sport... that unites the team, including clinicians, the basic scientists." — Dr. Tanner (35:37)

8. Crossover With Autoimmune Diseases

Shared Mechanisms: Insights from transplantation immunology influence treatments for autoimmune diseases (e.g., type 1 diabetes, IBD, RA), and vice versa.
- "Mechanisms that are similar between the rejection of an organ transplant and an immune mediated autoimmune disorder." — Dr. Thompson (30:34)
Hope for Broader Application: Advances in immune modulation may benefit a wide array of immune-driven illnesses.

9. Looking Forward: Hope and Next-Generation Possibilities

Lab-Grown and Gene-Edited Organs: Research efforts are underway to make engineered organs a reality.
- "In the future we should be able to grow organs or parts of organs in the lab... the progress has been very exciting in this field." — Dr. Tanner (32:39)
Shared Optimism: The field is driven by historical progress and continuous hope for better solutions.
- "I believe we will be less dependent on the conventional anti rejection drugs... approaches that have less side effects." — Dr. Thompson (33:24)
- "I would tell the patients that the progress is going to continue..." — Dr. Tanner (34:32)

Notable Quotes & Memorable Moments

On the paradigm shift:
"Where the field is going is toward selective suppression of the anti-donor response... being able to instill unresponsiveness specifically to the donor, which would be of great benefit to the patients."
— Dr. Thompson (03:55)
On side effects:
"Recently, the American transplant society did a survey in over 10,000 transplant recipients. And 92%... stated that they had at least one side effect of these anti rejection medications."
— Dr. Tanner (13:22)
On cellular therapy evidence:
"We have some encouraging signs that this intervention may be successful. However, we have to now undertake what’s called a randomized trial to formally test efficacy."
— Dr. Thompson (15:43)
On team science:
"Transplant is a unique treatment in medicine that involves two individuals, really connects two individuals... That unites the team, including clinicians, the basic scientists."
— Dr. Tanner (35:37)

Timestamps for Key Segments

| Segment/Topic | Timestamp | |---------------------------------------------------------------|------------| | Introduction and episode theme | 00:35–01:30| | The problem: immunosuppression and its trade-offs | 02:11–08:14| | “Holy Grail” of transplantation tolerance defined | 10:18–10:49| | Why the liver is special; advances in liver tolerance | 11:22–13:01| | Regulatory T cells and myeloid cells in tolerance research | 13:13–14:17| | Mechanisms: chimerism and immune system retraining | 18:14–19:46| | How infused donor cells communicate with recipient | 19:57–21:30| | Application to other organs beyond liver | 21:39–25:05| | Xenotransplantation and future sources of organs | 26:21–27:56| | Patient journey and perspectives | 28:18–30:12| | Crossovers with autoimmune disease | 30:12–32:23| | Future: lab-grown, gene-edited, and animal organs | 32:23–33:14| | Shared optimism and final thoughts | 33:24–36:16|

Conclusion

This episode provides a deep, hopeful look at the future of transplant medicine, where patients may one day be free of the burdens of broad immunosuppression. Through advances in cell-based therapies and greater understanding of immune tolerance—pioneered in liver transplantation and increasingly extended to other organs—researchers are making significant progress toward the "holy grail" of transplantation. The collaborative spirit among patients, donors, clinicians, and scientists is driving historic change, promising bright prospects both in transplantation and broader immune-mediated disease.

This summary captures the episode’s tone of scientific optimism, respect for the patient journey, and commitment to ongoing innovation.

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Transcript75 lines

[00:00]
A
Hey there. I'm Rachel Feldman and I host a podcast from Popular Science called the Weirdest Thing I Learned this Week. Every other week, I circle up with guests like Bill Nye, Josh Gondelman, Mary Roach, and many more to prove that the lofty and noble pursuit of science can also be profoundly weird. From flying Ford Pintos to the world's most illegal cheese, the weirdest Thing I Learned this week is the ultimate source for all things interesting, informative, and, and most importantly, frickin weird. Check out the weirdest Thing I Learned this week. Wherever you get your podcast, come on over whenever you're ready to get weird.
[00:35]
B
We're talking about trying to retrain the immune system so we don't have to just reduce the immune responses to anything, but just trying to reduce the immune responses to the organ itself so that we can re educate the immune system and mitigate the side effects that the immunosuppression drugs come with.
[00:52]
A
A donated organ can save your life, but from the moment it's placed inside your body, your immune system sees it as an invader and tries to destroy it. For decades, the solution has been powerful anti rejection drugs. But what if there's a new way? If we could teach the immune system to make peace with a transplanted organ instead of fighting it? That idea once seemed impossible, but now scientists are looking to the body's own own playbook, unlocking the liver's unique ability to promote immune tolerance and developing therapies designed to teach the immune system acceptance rather than suppression. That's what we're talking about on this episode of Tomorrow's Cure from Mayo Clinic, a podcast that brings the future of medicine to the present. Lindsey, I'm Lindsay Sievert. It's great to have you with us. Joining me are Dr. Timotin Tanner, a transplant surgeon at Mayo Clinic, and Dr. Angus Thompson, a transplant immunologist at the University of Pittsburgh Medical Center. Dr. Tanner and Dr. Thompson, it's so wonderful to have you both here for this conversation today. And before we get started, I heard you talking earlier and I understand that you're longtime colleagues. Tell me a little bit more about your capacity of which you've worked with one another.
[02:11]
B
Yeah, thank you very much, Lindsey. It's an honor to be here. We go back quite a while. Angus was my PhD advisor and mentor and has been my mentor ever since. I owe him a lot to what I became today.
[02:24]
C
For me, it's been extremely gratifying to see Dr. Tanner flourish in his career, becoming a leading, internationally recognized surgeon scientist who contributes continually to or organ transplantation. It's always been a great pleasure to have been his early mentor and to remain friends for many years.
[02:47]
A
Well, that is just wonderful. And before we get into this conversation, I'd just love to set the stage, since you both specialize in transplant medicine and started all those years ago. So for listeners, when they think about transplant medicine, many might just think about just the surgery itself. Many don't know that transplantation is really the beginning of a long relationship between a patient, a new organ and the immune system. And for more than 50 years, transplant medicine has relied on this trade off. You get a new organ in exchange for a lifetime of medication. But researchers are chasing what many call the holy grail of transplantation, A future where some patients may no longer need anti rejection drugs at all. So that's what we're diving into in this episode. And Dr. Tanner, can you just give us a short summary of the reason why we're talking today?
[03:37]
B
We're talking about trying to retrain the immune system so we don't have to just reduce the immunos the immune responses to anything, but just trying to reduce the immune responses to the organ itself.
[03:49]
A
Dr. Thompson, how would you give us your elevator pitch of that same advance?
[03:55]
C
As Dr. Tanner has said, we are currently highly dependent on anti rejection drugs that are nonspecific in how they affect the immune system. It's rather like a blanket suppression of responses to all foreign entities. Where the field is going is towards selective suppression of the anti donor response. And these approaches show significant promise in being able to instill unresponsiveness specifically to the donor, which would be of great benefit to the patients in reducing their dependence on non specific immune suppression and eventually becoming independent of these anti rejection medications.
[04:54]
A
While advances in medicine explore these different kinds of cell therapies, they all share the same teaching the immune system how to accept a transplanted organ. That way, patients may someday rely less on lifelong anti rejection medication.
[05:10]
B
Just to give you a scope of the issue, in the United States, about 50,000 people get an organ transplant every year. So if you add this up, it adds up to 500,000 people in 10 years. In the world, we're approaching 180,000 transplants a year. So this is the scope of the problem. This is a problem that the modern medicine created. Transplant was not available 50 years ago. Now it's readily available. It's one of the most successful treatments that we can offer.
[05:43]
A
So Dr. Tanner, at what point do immunosuppression drugs come into the picture and can you help us understand why they are such a central part of transplant care?
[05:52]
B
Immunosuppression drugs come in to the field right away, at the time of the transplant because the immune system works in a way that it's designed or evolved to react to anything that's not a self. Any different organ coming from a donor in a recipient's body will be seen as a foreign. It's got to have a lot of proteins that are seen as a foreign. So the immune system starts recognizing it within minutes and starts attacking it. So the immunosuppression medications are there to, to suppress that response, to modify it so that the organ does not have a rejection. If you don't control, this is what we call the rejection.
[06:36]
A
And that is a reality for many patients that do experience rejection or they, they can correct.
[06:42]
B
So unless the immune system is adequately suppressed, people will have rejection. Rejection may sound like a scary word, but once detected and treated adequately, it usually does not lead to long term consequences. But it needs to be treated with most of the time enhancing immunosuppression, increasing the dosage of the immunosuppressant medications.
[07:06]
A
And what does that look like for, let's just say a liver transplant recipient? Is it a daily pill? What kind of, what is, what kind of medication is it?
[07:14]
B
So let's say a liver transplant recipient, they start with a regimen of three different immunosuppressant drugs. They are all pills. They take this every day. And usually because of the liver's unique tolerogenic ability, we're able to reduce that to just one drug, one at night, one in, in the morning, after the first few months. But we don't have that luxury in other organ transplants. Most other organ transplants, including kidneys, lungs or hearts, people may need to continue taking two or three different medications throughout their life.
[07:52]
A
And these medications can have some tough side effects in some cases.
[07:56]
B
Correct. These drugs, as effective as they are, unfortunately come with some side effects. Correct. People may have increased incidence of infections, increased incidence of some certain types of cancers, and they also increase the incidences of diseases like diabetes and hypertension.
[08:15]
A
So let's say that someone receives a new organ. At what point do those anti rejection drugs come in? Is it immediately?
[08:21]
B
It starts immediately whenever we use an organ for somebody else. The organs, we all have different genetic makeup, so we all have proteins on our organs that are seen as a foreign by the recipient's immune system. So you have to train the immune system not to see that protein as a foreign antigen. So you have to start that at the very beginning, right at the time of the transplantation.
[08:49]
A
Dr. Thompson, we've all heard the stories of people waiting for an organ for so long. What do people misunderstand about anti rejection medicines?
[08:58]
C
It's important for people to recognize just how much enormous progress has been made, certainly in my lifetime from considering transplantation as something that really was not possible, to something that has become relatively straightforward standard of care procedure. I think people do appreciate that immunosuppressive drugs are effective. They do recognize that there are certain untoward effects that can accumulate over time. It's remarkable that we are dependent on the same armamentarium of drugs that we've been using for the past two to three decades or even longer. And that advances towards the holy grail of being able to minimize discontinue anti rejection drugs over time has proven a really tough challenge. Although many advances continue to be made that give us a great deal of hope that we will in the foreseeable future be able to get larger numbers of patients on very low doses of anti rejection therapy and even awful immunosuppression altogether.
[10:18]
A
What is the Holy Grail? I heard you say something. The idea that someday a patient will receive a transplanted organ without being on lifelong immunosuppression medicine. Is that what that is?
[10:29]
C
Well, yes. The Holy Grail was a term that was coined many years ago by immunologists and surgeons. And it's the vision that a state of transplantation tolerance can be achieved in patients. And by tolerance, the patient is able, at some stage post transplant, usually many years, to become a potential candidate for withdrawal of all immunosuppression. This is possible in liver transplantation where depending on length of time post transplant, it may be possible to cautiously withdraw immunosuppression from the patient and the patient does not reject. But that has not, as I mentioned earlier, been an easy thing to prospectively undertake.
[11:22]
A
Dr. Tanner, that holy Grail. The best chance of studying that holy grail or getting closer is, I heard Dr. Thompson say, is within the liver. So what work is underway at Mayo Clinic where you're studying this closer?
[11:36]
B
Yeah. So before that, let me tell you why the liver we think is special. Because liver is, through the evolution, just trained itself to not react to these proteins, these antigens, because it's constantly exposed to dietary antigens. So whenever we eat or intake something, it goes through the bowel and it gets absorbed and all that nutrients, they get into the bloodstream and that that blood goes through the liver. So liver is trained to see those antigens and not react to it. So it's just one of those evolutionary things that allowed us to come this far. Because of that, through many years of research, we know that the liver transplant recipients, just as Dr. Thompson said, are probably the first cohort of transplant recipients that we can try to achieve tolerance in. We have done several trials trying to get or induced tolerance in liver patients. And Dr. Thompson has done a very innovative trial at his place using those. The trials we have done at Mayo Clinic are those that involve infusion of cells into the recipient called regulatory T cells. So these are lymphocytes, or white blood cells that are in charge of controlling their counterparts. So they are the gatekeepers, so they control the other lymphocytes from attacking the liver.
[13:01]
A
As researchers at Mayo Clinic and the University of Pittsburgh test new approaches, they work towards the same goal. Retraining the immune system so transplant recipients could one day face fewer side effects and a better quality of life. Has this been a problem that you've been trying to solve as clinicians since you all the way since you worked in Dr. Thompson's lab?
[13:22]
B
I completely agree with Dr. Thompson's sentiments about the immunosuppression drugs and how it made us this successful. We recently had a 50 year celebration of our abdominal transplant surgery division and looking back, it gave us a chance to reflect on the progress we made in 1975 and kidney transplant recipients had about 30% of expected one year survival and we are now talking about over 99% thanks to these anti rejection medications. However, they do come with certain risks. Recently, the American transplant society did a survey in over 10,000 transplant recipients. And 92%, while they were very grateful and happy with their progress, stated that they had at least one side effect of these anti rejection medications.
[14:13]
A
So Dr. Thompson, tell me what's underway at your lab with this research?
[14:18]
C
For many years. This goes Back to when Dr. Tanner was doing research in Pittsburgh and earlier. We've been interested in a particular type of immune cell actually different from the regulatory T. T. Cells that Dr. Tanner has described. The cells that we are focused on are not lymphocytes, but innate immune cells of the myeloid, not the lymphoid system. And these cells have the ability to to very effectively regulate immune responses. So in the trials that we have been conducting in live donor liver transplantation, we generate these regulatory cells from the prospective liver donor and we infuse the cells before transplant or after transplant into the liver recipient. We follow the patients for a year, we perform what is called a protocol biopsy one year post transplant and if the patient is clinically stable and has no evidence of any ongoing rejection, we can cautiously begin to withdraw immunosuppression. And in some patients we have been able to withdraw immunosuppression completely. And then in following these patients, they have remained off all immunosuppression for three or more years post transplant. So we are encouraged by, first of all, the feasibility of doing the study, the safety of the cells when infused into the patient, and what we would call exploration of efficacy. We have some encouraging signs that this intervention may be successful. However, we have to now undertake what's called a randomized trial to formally test efficacy of the cell therapy approach to improving outcomes.
[16:25]
A
When researchers take specialized immune cells from the organ donor and give them to the transplant recipient before or after surgery, again, the hope is that these cells help recognize the new organ as something it doesn't need to attack. The science is still evolving, but the promise is significant. Researchers are now working to confirm those results in larger clinical trials.
[16:54]
C
Busy Healthcare Professionals this one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit ce mayo.edu podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by male clinic experts.
[17:32]
A
What is the breakthrough that allows some of the successful patients to withdraw from their immunosuppression drugs altogether?
[17:39]
C
These donor derived cells express the crucial donor antigens that are recognized by the recipient before transplant. And we believe that the cells bearing those donor antigens that also have an immune regulatory function teach the recipient's immune cells to be less responsive to the donor organ when it's transplanted into the body.
[18:10]
A
Dr. Tanner, what is the breakthrough here for you and your work?
[18:14]
B
This all shows me that we're getting one step closer every time we talk about this. There are several approaches. Dr. Thompson's approach has been very successful at Mayo. We are also trying to retrain the immune system of the recipients. Another way of doing this is trying to achieve what's called a chimerism. So if you can retrain the immune system by introducing the donor's immune cells into the recipient and they start to live together without attacking each other, then you can put that donor's organ into the recipient without having to worry about rejection because you had already retrained it. So that is done through infusion of stem cells that are obtained from the recipient. All these kind of approaches, including the regulatory T cell approaches, Are just taking us one step closer to achieving or getting to that holy grail that we've been talking about.
[19:07]
A
What was the term that you called it? Kind of teaching the cells?
[19:11]
B
Yeah, retraining the immune system is what I call it. It is really trying to retrain the immune system, because immune system evolves to fight against anything foreign to us. That's how we can survive infections. That's how we survive cancers, because what is not ours is foreign and we have to fight it. That's how the immune system works. If we can retrain it not to react to just specific proteins that are on the surface of that organ without changing its reactivity to infections or cancers, that would be the tolerance.
[19:46]
A
If we could look through a microscope, what happens when you introduce some of these donor cells to the recipient and they teach the other cells? How does that work?
[19:57]
C
Perhaps I can address that. Because our studies are specifically focused on infusing donor derived cells in the context of living donor liver transplantation. We believe that these cells, when they are infused into the body, actually don't survive very long, but they pass on messages to the recipient immune system. And these messages are, we believe, conveyed in the form of small particles, or vesicles, that are derived from the infused donor cells. And these particles, they're sometimes called small vesicles, extracellular vesicles, they convey the donor antigen, but in addition, they also convey instructions, protein molecules, and possibly also RNA molecules, that, when they are accepted by the recipient immune cells, condition those recipient immune cells to be unresponsive specifically to donor antigen, because the donor cells that were infused express the donor antigen. And studies that we've done for many years at the university of Pittsburgh do indicate that this is how the cells are instructing the host immune system to be less responsive or unresponsive to the donor organ.
[21:31]
A
When all this happens, when all these messages are received, what does the liver then do next? Or how is the liver sort of a clue that this is effective?
[21:40]
B
Yeah, liver has a way of retraining the immune system itself, but we have done several studies here at mayo clinic Showing that the liver itself, after the transplant, Changes the immune responses against it through working with the recipient immune system. That's how it tends to protect the simultaneously transplanted organs from rejection. When you do a liver and a kidney transplant, the incidences of rejection in the kidney are just much, much lower, despite the same immunosuppression. So we know that liver has that capacity, achieving that, as Dr. Thompson said, would allow us to just reduce the immunosuppression very controllably, slowly making sure there's no injury to the liver and eventually to completely get rid of the immunosuppression that people have to rely on. I think each of us are making progress through our own unique ways, trying to retrain the immune system. As I said at Mayo Clinic, we have several upcoming trials in liver transplant patients. But in addition to that, something we haven't talked about, we have started aiming at other organ transplants as well as. Just because liver seems to be a little easier should not lead to just working on liver transplant patients because everybody else also needs this kind of innovative approach. So we have infused cells into the kidneys of kidney transplant recipients with rejection to slow down the rejection, using or mimicking the biology, using some of the anti inflammatory cells to help us reduce the inflammation within that. Those have been successful thus far. As Bell and just like Dr. Thompson said, we are at the face of expanding those trials to do more efficacy studies.
[23:29]
A
Dr. Thompson, what is the potential, as Dr. Tanner just mentioned, of other organs, he mentioned kidney. What other organs could this be effective with? Or what are you studying there?
[23:40]
C
I think we have to recognize that while the spontaneous occurrence of transplantation tolerance is relatively common in liver transplantation, it is very rare, exceptionally rare in kidney transplantation, but it does occur. So these natural occurrences of transplant, clinical transplantation tolerance really encourage us to pursue the cutting edge approaches that we believe a step at a time will take us closer to the holy grail of transplantation tolerance. So kidney is clearly amenable to many of these innovative approaches to conditioning the organ or conditioning the recipient with innovative therapeutic agents, whether it's cell therapy, body biologics, new biologics or new pharmacological agents, the heart and lung where perhaps the greatest unmet need these organs. Clearly the patients would benefit from the same advances. And although it is more challenging, it is still possible to think about applying these approaches and thoracic organ transplantation.
[25:05]
B
Thoracic organ transplants, heart and lungs are life saving transplants. Day two need to be on anti rejection medications because the consequences of having a rejection in those organs are quite high. Then they are kept on higher doses of immunosuppression. So it would be great to be able to take these innovative approaches to the thoracic organs, as Dr. Thompson said. And I'm hopeful that we're getting closer and closer to that point.
[25:34]
A
I love what you said, that transplant medicine has become so refined and sophisticated over the past 50 years that in solving one problem we've created another. And now it's your moral imperative really to solve this other problem with immunosuppression medicine. Is that how you see it, Dr. Thompson? This is the new frontier for you as an immunologist?
[25:56]
C
Yes, as an immunologist, my career long goal has been to ultimately improve outcomes for the transplant patient, reduce dependency on anti rejection therapy and getting closer to the goal of clinical transplantation tolerance. We have a recurring very real issue of inadequate supply of donor organs.
[26:22]
B
That's a real issue and that has been a real issue ever since transplant has started. We simply do not have enough organs for people who are in need of organs. So a lot of progress on that has been made also. Part of that is thanks to the advances made in immunology as we've been talking about. And part of that is trying to find other sources of organs like xenotransplantation. Genetically modifying non human animals with similar sizes to humans to make them more suitable for transplantation. There's been a lot of progress in that in the last few years too. There are a lot of immunological issues that goes with that. But most of those issues have been tackled now compared to where we were 20 years ago. And that is becoming a reality in the next few years as well.
[27:14]
A
So xenotransplantation. So that's organs that are sort of modified from animals like you said, like pig.
[27:22]
C
Correct.
[27:22]
B
The most common source is pigs because pigs have very similar sizes of their organs as humans. So that makes sense. And genetically modifying these pigs to make them more similar to the human organs. The initial trials are on their way to start from probably with kidney and heart transplants. You might have heard or read the news about those things. Larger trials are coming in several centers, including Mayo Clinic, that will involve trying these organs in patients who are in desperate need of organ transplantation.
[27:57]
A
I'd love to bring it back to the patient. I hear a lot of excitement in where this is headed, but also a lot of careful optimism that you have to go, you have to take the next step and the next step. What have we learned so far from the patient journey? I know that there are still many patients out there trying to stop medications after years of what's known as tolerance focused therapy.
[28:18]
C
The willingness of patients to participate in promising clinical trials is very precious. And as clinicians and scientists, we are very grateful to patients and their families for participating in in these studies that offer, as Dr. Tanneha said, considerable grounds for optimism. And as transplant scientists, we, I feel, are entitled to be optimistic because of the incredible strides that have been made. And I think that inspires us, it inspires patients, and it inspires families to have optimism about the future of the field.
[29:01]
A
A lot of short daily news podcasts focus on just one story, but right now you probably need more on up first from NPR. We bring you three of the world's top headlines every day in under 15 minutes, because no one story can capture all that's happening in this big crazy world of ours on any given morning. Listen now to the up first podcast from NPR. Dr. Tanner, what what do you hear from patients that have received organ donations and what do they face?
[29:31]
B
Transplant recipients are very grateful to their donors. The first thing is that we cannot do any of this without the donor. So a lot of credit goes to donors, whether they are deceased donors or living donors. That is truly a gift of life. So that's number one. Number two, most recipients really are very proud of the process they went through to get a transplant, and they want to keep that transplant as long as it goes forever. And that's our goal as well. So our job is to help them do that. So all these efforts to try to reduce the immunosuppression, to get them off the immunosuppression is to help them get to that healthy life and keep that precious gift as long as possible.
[30:12]
A
Dr. Thompson, there is another link between what we're talking about today with transplant tolerance research, but also autoimmune conditions like diabetes, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis. So I'd love to hear how you're learning. What you're learning now can also have a lot of potential with autoimmune disease treatment as well.
[30:35]
C
Those of us who perform science and transplantation and perform science in the many autoimmune diseases share an understanding of mechanisms that prevail in both conditions. The immune response is an undesired phenomenon in transplantation and in autoimmune diseases. And the two fields do learn and are instructed for one another. The development of immunosuppressive drugs in the field of transplantation led to their application in numerous autoimmune disorders. And similarly, the successful trials of immunosuppressive agents in the field of autoimmunity can be instructive for transplantation. There have been quite a number of examples of this two way relationship. One field learns from the other reagents that may prove new agents that may prove to be very Effective in controlling certain autoimmune disorders, may be valuable for testing in organ transplantation, that overall there are many mechanisms that are similar between the rejection of an organ transplant and an immune mediated autoimmune disorder.
[32:05]
B
Yes, I completely agree with all that. So immune system plays a major role in a lot of disease processes. So while transplant is allowing us to study this in a sort of a man made disease condition, the findings are helping other patients like those with autoimmune disorders.
[32:24]
A
I'm just curious, when you look decades into the future, what research implications are there beyond today's transplant patients? I'm thinking about lab grown organs, gene edited organs, or other technologies that we're just beginning to explore.
[32:39]
B
Those are all on the table and a lot of people are working on different parts of this whole progress. In the future we should be able to grow organs or parts of the organs in the lab. We should be able to adequately modify the genetics of animals or lab animals that we can take their organs from and transplant into people. Hopefully the field will look much different in the next 30, 40 years as it looks different now compared to 30, 40 years ago. I think the progress has been very exciting in this field.
[33:13]
A
Dr. Thompson.
[33:14]
C
Yeah.
[33:15]
A
If these advances continue to move forward, what does this mean for patients and families living with the realities of transplant today? And what do you hope for? What do you imagine?
[33:25]
C
I think these advances instill enhanced optimism about continued progress. There's a remarkable shared vision between clinicians, scientists and donors, graft recipients and their families. And this shared vision is something that I personally feel really does help sustain the field. So if we think a generation ahead, I believe we will be less dependent on the conventional anti rejection drugs that we've been dependent on for so many years. And we will be using approaches that have less side effects, cumulative side effects over time.
[34:14]
A
Thank you so much. And Dr. Tanner, as Dr. Thompson was speaking, I was thinking just what promise or what hope is on the horizon as a gift to your patients who have really been through so much, to be able to tell them there is something around the corner has got to keep you hopeful as well.
[34:33]
B
If you take a step back and look at the transplant process, you realize that how much progress has been made over the past 50 years or so, I would tell the patients that the progress is going to continue. Thanks to the donors, we're able to do all these studies, adding scientific data to their care and this is all ending up with better and better graft survival, better patient survival, and we're very optimistic about the future in transplant Medicine.
[35:03]
A
In our podcast, Tomorrow's Cure, we really focus not only on innovation, but that that grounded sense of hope. And I'm just wondering where you're at with your studies and your research. What gives you hope and maybe a little bit of wonder about the future of transplantation?
[35:17]
C
I think that the history, the developments, and the shared optimism about the future are what will continue to drive this field forward.
[35:28]
A
Yeah, Dr. Tanner, it really is this ecosystem of care all the way from the person who decides to give their organ all the way to this moment.
[35:37]
B
This all goes back to transplanting being really a team sport. There are some things in medicine that involves just the patient and the treating physician. Transplant is not one of them. Transplant is a unique treatment in medicine that involves two individuals, really connects two individuals. The donor and recipient comes with a whole team that supports the success of that transplantation and that unites the team, including clinicians, the basic scientists. That gives us hope that this will continue to improve and the outcomes will be much better than what they are now, which is still fantastic.
[36:17]
A
Wonderful. Well, thank you both so much for your history of collaboration, for your research, and for enlightening us today. I really also approach this field with hope for all the patients who have been through so much. So thank you. Thank you again.
[36:32]
B
Thank you very much, Ninzi.
[36:33]
C
Thank you. It's been a privilege.
[36:36]
A
Tomorrow's Cure is a production of Mayo Clinic with production help from the Podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts. And if you liked today's episode, please like and subscribe. I'm Lindsay Siebert. Thank you so much for being with us.