From Joint Damage to Regeneration | Tomorrow's Cure Season 5 Episode 5

[00:00:00]Reclaim was an open procedure in the knee, but it pushed new limits and frontiers and it improved patient care.

[00:00:06]We were able [music] to develop an arthroscopic technique to be able to apply it in the hip. Then now arthroscopic [music] reclaim can start circling back to the knee and then now we start saying, well, what else? How else can we improve? Knee patients, hip patients, big toe patients. The fact that we get to [music] challenge each other and show each other our challenges really makes us into a better and a more cohesive whole and I think in the [music] end all you want to do is treat our patients better and and the patient ultimately >> benefits. A sore joint [music] hurts.

[00:00:32]Most of us know the feeling. Sometimes it's wear and tear and other times an injury. But when cartilage [music] in a hip or knee is damaged, the body has a hard time rebuilding it. And for many active people that can mean pain, loss mobility, and tough choices [music] for what comes next. Now researchers at Mayo Clinic are working on a different kind of repair. It recycles a patient's own cartilage [music] cells, combines them with donor medicinal signaling cells, and delivers that mixture back [music] into a joint in a single procedure. The approach is called reclaim. It points [music] to a future where cartilage repair may become less invasive, more precise, and more [music] practical to deliver. 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 [music] to the present.

[00:01:27]I'm Lindsey Seavert. It's great to have you with us. Joining me are Dr. Daniel Saris and Dr. Mario Hevesi from Mayo Clinic, along with Dr. Christian Lattermann from Mass General Brigham.

[00:01:38]Together they bring a collaborative perspective on what it takes to turn regenerative medicine from an idea to reality.

[00:01:45]Today we are talking about a really frustrating reality in orthopedic medicine, cartilage damage. We all know that can change someone's life, but repairing it can often mean a lot of complicated procedures, long recovery, in some cases more than one surgery. And now a new approach that will be chatting about today called reclaim can really change the future of that reality. I love the name reclaim. It's like you can reclaim part of the activity you wanted, the life you wanted, but also the cells are reclaiming their strength. So, Dr. Saras, we'll start with you. You're a knee expert.

[00:02:21]And for those listeners who might not know a lot about cartilage injuries, why is cartilage so difficult for the body to repair once it's injured or damaged?

[00:02:32]>> You know, Lindsey, that's actually a really interesting question, and I don't know for sure if we or science actually has the answer to that.

[00:02:39]What I sometimes think is that cartilage is so well designed to do what it's made for, but mother nature or whoever developed us forgot to put in something for a repair and regeneration.

[00:02:50]So, your bones always heal because if you couldn't run away because your bone was broken, you got eaten. So, evolution took care of people with bad bones. But evolution didn't care about people with bad cartilage yet. So, we're still trying to figure that out scientifically. And if you have damage in your cartilage, it's like having a pothole in the street. That's how I explain it to my patients. There's a big pothole. If you keep driving over it, it tends to get bigger and it tends to damage until the sparks fly. And that's where the science and the clinical reality come in.

[00:03:18]>> And Dr. Hervey C, you specialize in hips. I mean, same story with the hips.

[00:03:22]Hard to repair the cartilage. Got a pothole situation in our hips, too.

[00:03:27]>> Exactly. So, I think cartilage, same material, same asphalt, if you will. A really, really smooth asphalt. We want to have smooth cruising. And the hip is unique in that in terms of cartilage, it's hard to access cartilage. Your knee is skin deep. You can touch your knee.

[00:03:41]You can feel your knee, but you can't quite touch your hip joint. And so, many people have deep groin pain. They have pain with walking. But unfortunately, without some type of intervention, cartilage does not heal itself. and that's that's where we come in as orthopedic surgeons. Now with RECLAIM, we can feel that we're providing the standard of care surgery, that hip arthroscopy, that labral repair, that we have always provided, but finally we can address that missing piece and address that articular cartilage or that cartilage defect that we used to not be able to do much with.

[00:04:11]>> For years, orthopedic surgeons could correct many of the structural problems causing hip pain, but one piece of the puzzle remained stubbornly out of reach.

[00:04:20]Repairing damaged cartilage itself, which for many is a continued source of pain.

[00:04:26]>> Can you talk through the patient experience of the ones that you've worked with so far of what exactly happens? You know, are they put under?

[00:04:32]Is it a simple like outpatient procedure? Talk about how it works, and then how does that compare to the standard treatments available?

[00:04:40]>> So, RECLAIM I would think of as an augmentation or as a value add to how we are addressing other underlying issues.

[00:04:48]In the hip, these patients usually have a reason of why they develop their cartilage damage. They have an aspherical ball, the ball looks more like an egg rather than a sphere. They have a pincer, their rim is their socket is too deep. And so, those are things that we've historically surgically addressed, although that's relatively new of repairing labrums and doing hip modern hip arthroscopy really took off in the past 5-10 years. But, historically we didn't look at the cartilage defects, we documented them, we might have debrided them or just smoothed them. And then from my perspective from a hip population, I would highlight that >> These patients are getting hip arthroscopies to treat their other reasons why they might have had their cartilage damage.

[00:05:25]>> And RECLAIM does not slow down their recovery, and to Daniel's point, I do think that experiencing these patients in the clinic, they tend to look clinically better and to be ahead of the curve, but our usual hip arthroscopy patients are on crutches for 4 to 6 weeks to help actually protect the other repairs that we do. And RECLAIM does not slow that down, and these patients are on a similar timeline in terms of the formal restrictions that we give those patients.

[00:05:46]>> RECLAIM isn't designed to replace everything orthopedic surgeons already do. Instead, it becomes part of a larger strategy to restore the entire joint.

[00:05:56]Surgeons often correct other problems at the same time, creating the best possible environment for healing, which expands the power of Reclaim.

[00:06:05]>> I think one thing that is important though and that needs to be understood and not all of these patients are just having Reclaim.

[00:06:15]They often have additional procedures that are done at the same time, particularly around the knee. We often change the actual alignment and means you add additional surgeries to change how the knee is loaded. These are called osteotomies. Or you do other things like, for example, you have to replace a meniscus that is missing.

[00:06:35]Because otherwise another part of the joint is missing and is not around and will not allow Reclaim, as good as it may be, to fully do its job. And those actually are probably the bigger determinant now in terms of the rehab process.

[00:06:51]>> I love that and I really would like to highlight that of the coming full circle but then coming circle again is so gratifying and great to be able to be part of. Reclaim was an open procedure in the knee, but it pushed new limits and frontiers and it improved patient care. We were able to develop an arthroscopic technique to be able to apply it in the hip. Then now arthroscopic Reclaim can start circling back to the knee and then now we start saying well, what else? How else can we improve?

[00:07:16]>> From a patient perspective, the surgery and this procedure Reclaim is different than what has been available before. The surgery at the moment takes anywhere between 70 and 90 or 120 minutes depending on the preparation of the cells. And hopefully, as we spoke about before, this can be accelerated because we're creating a situation where a black box technically can do the stiff that now has to be done by hand in a lab, and that would mean it would be a much simpler procedure. What we've seen in the data is that because it's a single surgery and because it's arthroscopic and probably because the MSCs improve the inflammatory environment in the joint, these patients seem to recover quicker by a a few months compared to the traditional patient population that have these surgeries. And by a few months I can say maybe 4 to 6 months of overall recovery for return to performance is what we've been seeing now. And traditionally I wouldn't venture out to say to a patient that they'd be back on the field or back in their full activities before 9 to 12 months. So that makes a big difference in this patient population.

[00:08:22]>> Dr. Latterman, you you specialize in sports medicine at Harvard. What's the bigger picture here? Dr. Saris talked about the knees, Dr. Hevesy talked about the hips.

[00:08:32]>> Articular cartilage is part of a system inside the knee, and the knee really functions much more as a combined system between multiple different tissues.

[00:08:41]And this is why just simply filling the pothole is okay, but that doesn't solve the issue completely. And this is I think where we are. We have lots of technology right now that allows us to fill potholes, but we have very very few basically no technology that allows us to actually modify whatever we are implanting there to improve the overall situation inside the joint. Because let's face it, before a knee joint becomes symptomatic from a cartilage injury, there's other things that happen beforehand and they often have to do with gradual loss of the cartilage architecture, not only in the pothole, but also in the surrounding areas, and that means cell death. And this is I think where some of the invention and the ingenuity of the Reclaim product comes in because you are actually repurposing, so to speak, chondrocytes that are sitting inside that joint and you are resetting the stage biologically. And I think this is extraordinarily unique and it may also be the key to why this could work in the hip because in the hip you don't have large potholes. The hip cartilage is really thin.

[00:09:59]>> So to set the stage to understand the innovation of reclaim, it's important to know that our own cartilage provides the building blocks, but receiving recycled cartilage cells alone aren't enough.

[00:10:11]They also need the biological signals that tell them how to grow and heal.

[00:10:15]That's where donor stem cells, known as MSCs, come in. Dr. Saras, I would love if you could tell us how all of your expertise, your your worlds, your specialties have converged. So I'm wondering if you could tell us what is reclaim?

[00:10:28]>> Yeah, thank you for asking and thanks for giving the opportunity to to spread the word and talk to people about it. It is the idea of recycling chondrocytes and cartilage cells. Like Dr. Latterman just said, these cartilage cells are from that joint. That's where they live and that's where they function until they didn't function that well anymore and the tissue was lost. So what reclaim does, it recycles the cartilage from the defect. You don't have enough cells and the cells don't have the right signals to grow cartilage and make the cartilage function properly.

[00:10:55]So then we came up with the idea of using allogeneic donor cells. So for all intents and purposes, we can call them stem cells or we can call them MSCs and we said, "Well, we need signals from those MSCs to provide the chondrocytes with a growth potential, but also to clean the tank in the joint to make sure that the joint homeostasis, the environment in the joint, is more conducive for cells to feel happy there."

[00:11:20]And that's why the combination of the recycled chondrocytes from the patient themselves with the MSCs from the donor bank, the allogeneic MSCs, together form this process that we call reclaim and all of that can be done in a single procedure nowadays, which is a big step forward because in the past patients for this indication used to have two surgeries. The cells went to a laboratory, or it was a transplant with tissue from a donor.

[00:11:44]And all of these solutions have good clinical outcomes, but they all have drawbacks, and we're trying to make it better from a patient perspective and make it better from a scientific progression standpoint as well.

[00:11:55]>> So, Dr. Sears, I just want to make sure that I'm understanding this right. So, you take the patient's own cartilage cells. They're mixed with these donor signaling cells, kind of mixed together, and then delivered back into the patient. I'm simplifying it, but >> No, that's exactly what it is. You're You're spot on, Lindsey. And you know what the interesting thing is? When you take the cartilage, we take the cartilage from the rim of the defect that has to be cleaned anyway. So, we clean up the defect, so you have a nice sharp environment that hopefully going to be a nice environment for this cartilage to fill the defect, so to speak.

[00:12:26]And then we chop it up in little pieces, so that there's a larger surface area to work with.

[00:12:31]Then we develop this chemical potion that allows us to digest the tissue to the smallest pieces of the cartilage cell, the chondrocyte, with a little bit of the matrix around it, which it uses to communicate with the environment.

[00:12:42]>> So, just to review, the cartilage cells, the chondrocytes, are essentially worker and builder cells that become stressed and inflamed.

[00:12:51]The MSCs, or donor stem cells, calm the environment and send chemical signals that let the cartilage cells start repairing tissue again.

[00:13:00]One of the biggest misconceptions about stem cells is that they simply become new tissue, but that's not how these donor cells work. Instead, they act more like coaches or teachers, so the patient's own cartilage cells can begin repairing the joint.

[00:13:15]>> In terms of the magnitude of the breakthrough, I think this is one of those pretty critical findings that had to be made in order to move the entire field to the next level. You know, other than what you often hear in the press that mesenchymal cells signaling cells or, you know, wrongly call them stem cells, they do not just go somewhere and build new tissue and then magically everything is healed. What they do do is they go inside an environment and they basically moderate the environment. I like to use an analogy is basically think about a room full of unruly kids and then in comes a favorite teacher.

[00:13:57]And the favorite teacher basically organizes these kids so that they behave. And that's kind of what MSCs do.

[00:14:04]And these chondrocytes, they are all upset because they are under inflammatory conditions. They are kind of to a certain degree mechanically impaired. And these MSCs essentially kind of sort of create the environment in the background that the chondrocytes can kind of sort of start reorganizing themselves.

[00:14:21]And this is really I think where it becomes uh serendipity. It would have been horrendous if we needed 90% autologous cells and 10% allograft cells or allogenic MSCs because we don't have that much autologous tissue to cover these defects. But it's actually the other way around. You only need 10 to 20% in order to cover the defect and the rest is being made up by your allogenic cells. And that is absolutely doable and achievable. And I think this is where the beauty of the approach comes in.

[00:14:53]>> I love your favorite teacher analogy cuz it really helps illuminate what feels complicated to someone like me who doesn't work in medicine. But essentially that favorite teacher or the the signaling donor cells remind the other cells that are damaged sort of how to behave. Right? Or how to repair. Like they calm down, reorganize.

[00:15:13]>> Yeah, they they basically give them guidelines so to speak.

[00:15:16]>> Dr. Hevesi, how does this all relate in in the hip as well?

[00:15:22]>> So, I think the hip is a special place that we can apply the innovation that came from Daniel's work in that historically hip has been hard to access. The hip is deep. It required a surgical hip dislocation. And that's that's very invasive for patients. Hip arthroscopy or keyhole surgery or minimally invasive surgery with long instruments through small little portals has really taken off. And that has allowed us to address a lot of the causes for unruly children or chondrocytes in the hip. So, femoral acetabular impingement FAI, that's the ball not being quite a ball but being more egg-shaped can really lead to some damage on the socket side.

[00:15:57]That's something that we can address, but in the end we still need that teacher to come in and make those cartilage cells grow and repair.

[00:16:03]And the fact that Reclaim is something that's injectable has really really changed the game because suddenly you can use the long needles and you can create a healing environment. You can fix a torn labrum. You can make a hip perfectly spherical. But now having solved all the reasons why you had early wear and tear arthritis, you can then address the cartilage itself and you can inject it because you can inject something that's deep down inside whereas you might not be able to use some other type of cartilage implant that's larger, blockier, you just can't get deep down in a minimally invasive manner.

[00:16:34]>> And is this a treatment, whether it's in the hip or the knee, that's utilized when you're kind of sore and uncomfortable before you head towards a like a full joint replacement or is it used in tandem?

[00:16:45]>> We're all sports docs and everybody has their own special joint, but we all try to intervene with these before they become fully arthritic. So, these are solutions, these cell-based technologies are joint preservation solutions. So, trying to have patients have their own joint with their own joint function for as long as we can until we need to convert to a total knee or a total hip replacement, which is still very good solution for the right patient at the right time.

[00:17:11]But if you're 22 and you have an ACL tear and you blow out a piece of cartilage, then this would be a solution to fix the joint so you can function with your own joints for 5, 10, 20, maybe longer years. And that's one of the things that motivates all three of us and the whole field. It's a team effort. Just like we do team sports, the team clinical and the team science together make these innovations better.

[00:17:36]And instead of becoming a solution for a pothole, it's become much more of a platform technology for tissue repair.

[00:17:43]And it doesn't just work in the knee and it it works in the hip. We also have some indications to consider it maybe for the rotator cuff in the shoulder or for the meniscus, which is also a shock absorbing tissue, or for the intervertebral disc in your spine. So now the science progresses us to other applications which are still under development. But like I said, it's a team sport in favor of the patient's benefit.

[00:18:04]>> Team sport, Dr. Lattermann, Dr. Saris mentioned your lab and the research that you are doing. So how are you taking Dr. Saris's innovation with Reclaim and applying it with your own research?

[00:18:14]>> I look specifically into inflammation and how inflammation resolves in an arthritic or early arthritic joint.

[00:18:22]And this is often driven by an initial injury and then a progressive loss of articular cartilage.

[00:18:30]And so I look more into clinically relevant solutions to reduce the overall inflammatory components. Where it becomes really interesting and where it really connects very directly is that you need factors to drive this inflammation resolution. And MSCs are known that they have the ability to send the appropriate signals for that.

[00:18:53]Traditionally, we have tried to do articular cartilage repair procedures with membranes, with plugs in the hip and they pretty much all failed because you typically need to do what's called a surgical hip dislocation. So you basically have to dislocate the entire hip and then you try to to it just like we've learned it in the knee or sometimes to a certain degree we do that in the ankle. But it just doesn't work that way because the hip joint and the particularly the underlying bone in the hip is constructed completely differently, and therefore the work that has to be done on the actual surface has to be different. And it cannot just basically fill a pothole. It has to have biological power, and I think this is where Reclaim has a significant advantage over anything else that I currently see out in the literature or in our clinical practice.

[00:19:45]>> I understand you're saying that the knee is pretty accessible, but once you saw the success that was happening in a hip, which is far more complicated to get the treatment to, then then you realized that the applications were pretty wide open.

[00:19:58]>> In situations like this, or at grand rounds, or even at our basic science lab meeting, some of the students or a fellow comes up and says, "You know, couldn't we try this for this and that situation?" So, literally as we were discussing Reclaim at the department meeting at some point, the shoulder and elbow team came up and said, "You know, we have patients that have problem healing their rotator cuff, at the tendon repair in the shoulder. Could your combined technology with the improved signaling from the MSCs and the repurposing of cells as part of a repair tissue be applied to the shoulder?" And then it sparks a whole new line of research.

[00:20:32]>> I think Lindsey, one one of the things here which which is very clear is is that the technology is really more platform. And and the the true innovation here is is not that you use chondrocytes to repair articular cartilage. The true innovation is is that you use autologous cells, mix them with allogeneic mesenchymal cells, and that is a very powerful concept, and that is a powerful platform that is probably extendable into other areas. It just happens to be that Daniel is one of the foremost cartilage researchers in the world, and therefore that's the first thing we have tried it out.

[00:21:08]>> One of the ways we thought of this has to do with research that was being done by others. So, Dr. Sekiya, a Japanese scientist, was doing some work on MSCs in synovial fluid. And they published a paper where they said when a joint is damaged, you can measure more or less synovial fluid and the content of the synovial fluid changes in its concentration with these MSC cells.

[00:21:33]And then we actually got in touch with him and they said, "Well, if if that's true for arthritis, is it also true for maybe when patients tear their ACL or when athletes have a meniscus tear?" And they hadn't necessarily thought about that yet. And then they did a follow-up experiment and they said, "You know what? Yes, that's true. If you damage your joint, there's an influx of MSCs.

[00:21:52]So, these cells go to the area where something's damaged to do something."

[00:21:56]>> So, we are learning that the real breakthrough of Reclaim may not be the cartilage itself. It's essentially a new biological playbook for healing damaged tissue, one that researchers are already beginning to explore far beyond the knee.

[00:22:10]>> So, I think that, you know, none of us does well in a silo. And to that point, this highlights the fact that team science is always better than individual science. And if you have a solution in the knee, then that's something that you should take to new frontiers and you should see how you can apply it to the hip, to other frontiers, to the meniscus in the knee rather than the cartilage.

[00:22:30]And the more we talk and the more that we interact as a scientific community, as a community of physicians, the more you can generate new techniques and new applications of a technology. And so, I love working together with Dr. Saris and people like Dr. Latterman where someone innovates in a certain field and shares that with you, publishes that, and you say, "How can we take this to the next level? And how can we apply it to your problems?" Because although we live different lives as orthopedic surgeons, we live similar lives and many of the things that one person struggles with treating or feels that they this should be not struggle, but it should be better treatable are the same things that apply in different joints or in different pathologies.

[00:23:06]>> Mhm.

[00:23:07]>> And it also ties together, if I may, because they developed the surgical technique. Dr. Krich, one of our other hip surgeons and my co-conspirator in the lab, and Dr. Evazi developed the surgical technique. And for that, we had to figure out ourselves, okay, being in a long syringe and do the shear forces damage the cells in any way? And they don't. And these are very simple experiments, but they have to be done.

[00:23:30]And that now allows us to translate that back to the knees. Even though you can do a small incision in the knee without too much struggle, we don't have to anymore. It could be a fully arthroscopic technique, and some patients will prefer that because it allows them to recover maybe quicker.

[00:23:43]Some doctors will prefer that because they're more familiar with arthroscopic techniques because the whole field is developed in that way. And that accelerates the implementation. It also makes the safety and the acceptability for the patients much higher. And therefore, the results of the outcomes are better again. So, it really is a cross-pollination team effort, which makes it fun. And the patients also become part of your team because these are experiments. Nobody's done this before. So, you have to have the trust, and they have to be part of the team to buy into being the first that has this done to them. And I'm still in touch with my first patients that ever had their MSCs transplanted. And this is a large responsibility, but it's also a really fun game to play together.

[00:24:21]>> Well, that's what I was going to ask you in these experimental treatments with some of the first patients or as it's evolved, many patients, what are they reporting to you? What are they feeling?

[00:24:30]>> These patients really do very well. Out of the first patients that we did 10 years ago, there's only one patient that had subsequent surgery, and most of them are still doing well.

[00:24:39]All of the patients that we treated for the RECLAIM study at Mayo Clinic have been followed up, and all 25 were safe, and all but two have had great clinical results now up to 4 years. So, from a clinical perspective, we know that the patients do well, but in the end, it's about the 10, 15, and 20-year data if it really makes a difference in the clinical practice. It's not about the short win, even though the scientific novelty also has very great merit to my extent.

[00:25:05]>> When you are doing these kind of procedures with your patients, this is really a collaboration with your patient and not just a treatment.

[00:25:14]Interestingly enough, most patients who are seeking out treatment like that are extremely excited about it and they actually specifically seek out those kind of treatment approaches, which is interesting because we typically get taught basically that you shouldn't take any risks whatsoever and these patients are willing to take those risks as long as the communication is good and as long as it's explained to them.

[00:25:40]And that on the back end, however, requires people like Dr. Saris or Dr. Hevesi or myself to spend a lot of time with these particular patients and this is what makes it sometimes very difficult to really move those kind of studies through.

[00:25:54]>> It's important to highlight the patient-physician relationship for these trials. I think it's very special because you get to see them more often than you might see other patients. You get to see them for longer and you see them change. Some of those patients have now had kids, they've changed jobs, they've graduated and it's so gratifying to see them go back to things that they'd like to do from a hip and knee perspective and see them one, two, three years later. But, it's also worth highlighting the fact that we are collaborative as Dr. Lotman said with our patients. This isn't a problem that has a good solution and we are just experimenting on another way to fix it.

[00:26:28]This is a problem that didn't have a good solution and you can have frank discussions but important discussions with your patients of in the hip world, right? You need a surgical hip dislocation to address your cartilage problem. Tell patients that's like telling you that the only way to change a spark plug is to take out your entire engine and put it in another room. That is way more invasive than getting a hip arthroscopy and just replacing your spark plug in situ. And you say that this is a bad problem. We think we have a better solution and we didn't dream it up yesterday. We dreamt it up collectively 10 years ago and beyond 10 years ago. We have our laboratory data.

[00:27:02]We have this great data from Utrecht.

[00:27:05]This is a stair step that has been being built for over a decade and now it's ready to be put into patients understanding that everything carries risks and benefits, but this is something that has been pre-contemplated on and tested at every step of the way and we think it's ready for you in a setting where there's no other good alternative >> or we think that this is the best alternative and that's why we'd like to try it. And Christian, I have a question for you. Do you think we'll ever be able to understand the phases of inflammation and the profiling of patients to be able to say which patient can be most well-timed for this sort of therapy at what point in their disease or their damage?

[00:27:43]>> To tell you the truth, maybe 5 years ago I would have told you I'm not sure that we will ever be able to do that because the individual steps sifting through all kind of different data sources and everything really were not available.

[00:27:56]Now AI is really changing that picture, right? The power of AI is incredible.

[00:28:02]As long as it is being utilized meaningfully and I think the most important thing here is that we are creating good databases that can be looked at and I think that is also starting to come together. There's more and more startup companies that are specifically looking into proteomics into DNA snips, into epigenetics.

[00:28:23]These are all kind of terms that are influencing how our cells basically run their day-to-day business so to speak under different conditions and that data exists and AI is able to pick up patterns here that we manually cannot really pick up. This is just beyond our vision.

[00:28:44]>> Could you give an example of that of how AI might [clears throat] interface with Dr. Saras's Reclaim treatment.

[00:28:50]>> Yes, so if you were to take his Reclaim technology, for example, you can take little samples of that and you could analyze those cells very carefully. You could do single cell RNA analysis on it.

[00:29:01]You can do biomarker analysis on it and you can correlate that with the clinical outcomes. You can correlate that with all kind of other genetic markers of the patients themselves, age, epidemiological data, etc. You throw all this together into an appropriately designed AI and what it will do, it will basically sift through all this data and make all these correlations and does regression analysis, etc. Stuff that if you do this manually will take you hours to do. It does that in seconds and will say, "Okay, there's a correlation here that's interesting. These correlations down here don't really show anything interesting." and it will basically direct you much quicker towards where you have to look.

[00:29:45]>> Our scientific team was smart enough to warn us to save samples from every patient. So, from every patient that was treated both in Europe and at Mayo Clinic we have samples of the original chondrons, we have samples of the MSCs, we have samples of their synovial fluid and now we have samples of their Apple Watch or their Fitbit or their Whoop or whatever device on how they're functionally doing, how active they are.

[00:30:07]We have imaging data. So, once we have all of that in an a well-designed AI agent, we can maybe come up with some of those interesting answers for my patients with knees and for Dr. Hevesi's patients with hip problem.

[00:30:21]>> So, another 10 years out if you clear all the hurdles that you'd like to clear and all goes as you wished or worked hard for, where would you like to be?

[00:30:30]Where do you see this?

[00:30:31]>> I'm going to say 3 to 5 years, Lindsey.

[00:30:33]We're not going >> Okay.

[00:30:34]>> We're not going to go that far. Come. We need accelerate this. So, what we're working on now at the moment with help of the Genesis initiative and the support by some of the wonderful possibilities that Mayo Clinic develops for to develop the tools that this can be done in any hospital.

[00:30:50]Hopefully in 3 to 5 years we will have an FDA approved Reclaim box that does the cell recycling, that mixes this with the allergenic MSCs. So this can be done in local hospitals and it doesn't need a Harvard or Brigham and Women's or a Mayo Clinic. It doesn't need a cell culture facility anymore because it's stand-alone a situation that the doctor can operate with maybe a little bit of technical support right where the patient has their care. So it becomes available to a wider audience in a safe and a reliable manner.

[00:31:22]>> And I imagine there'll be a lot of listeners out there living with some joint issues that that think, yeah, as we talked about earlier, how do I know if I'm the right candidate and when could this be available to me? I know that we still have some hurdles to clear, but what would you say to the patients that are wondering if they fit with Reclaim?

[00:31:38]>> Yeah, this is a solution that is for non-arthritic joints. So if you have arthritis and you don't want a knee or hip replacement yet, this is not the solution yet. But if you're an athlete and you just got damage or if you're a person who has an active lifestyle and your hip or your knee or your shoulder are keeping you from doing that because there's damage, we're developing programs. Here at Mayo Clinic we have an email address that is [email protected] and people can send us questions and we will screen them and we'll try to provide a relevant answer.

[00:32:09]>> In tomorrow's Cure in the Show, we really try to leave people with a sense of hope and possibility and certainly our conversation has been overflowing with that. But I wanted to ask each of you what keeps you most hopeful right now on the cusp of this treatment as a paper is about to be released looking at the 3 to 5 year plan. And Dr. Vessie, I'll start with you. What keeps you most hopeful about developing this treatment and in the work you do as a hip surgeon?

[00:32:33]>> What keeps me most hopeful is the trajectory. Honestly, we didn't have this as a procedure as a FDA phase one trial, which it started off in the knee 5 years ago. And in the past 5 years, if I'm looking into the next 3 to 5 years, we were able to implement it in the knee. We had 25 patients undergo it.

[00:32:51]Sitting here today, if I think about what we were able to do 5 years ago, it looks like a brand new world. And my true hope is that 5 years from now, I look back at this podcast and say, "What an amazing podcast, but we were doing such simple things back then. We have such deeper understanding and we're further able to take it to the next level." And clearly, where the sky's the limit there. It's amazing what we've accomplished in 5 years, and I think it'll be even more amazing what we accomplish in the next 5 years.

[00:33:17]>> What about you, Dr. Saris? What keeps you hopeful?

[00:33:19]>> I'm hopeful, I would say, for three reasons. One, we have great support to take this from a clinical reality to a clinical availability for a wider group of patients and providers, and that's very important.

[00:33:33]I'm very hopeful because we get to work with a bunch of young, smart people that come up with great questions, and we have an integrated team of basic scientists, clinician scientists, like the three of us, that come up with better solutions than a few years ago, and that will only accelerate. And as we learn more about the basic science of cells communicating with each other and Reclaim working for different tissues, the technology, as we just described in how we measure biological environments, the data processing, and our understanding of smart technologies to analyze large groups of data will make us much more effective in the questions we have to answer. So, there's hope for those three reasons, and I'm really looking forward to those exciting times.

[00:34:15]>> Thank you. Dr. Lattermann?

[00:34:17]>> Let me take that kind of a step back and look at this what happened in the last 5 years. So, what happened in the last 5 years is we have gotten a lot more understanding, particularly in in the area of joint degeneration in terms of what is driving it, what are the molecular backgrounds to it.

[00:34:38]We are no longer hunting for markers that are unspecific. We know very specifically what to look for.

[00:34:46]We have learned to utilize technologies out of other fields and we have learned from other fields.

[00:34:52]>> I had one curiosity of just with the general population living longer. My mother's almost 80 and in her friend group it's always the conversation will so-and-so is getting a new knee and so-and-so is getting a new hip and it's just kind of synonymous with aging and living well and living longer. How do you see that this treatment entering that landscape of joint replacement or just giving people more options as they live longer?

[00:35:13]>> There is a little bit of an age component even with MSCs and with all of our natural cells, right? We do know that every single one of our cells undergo aging.

[00:35:24]And you can actually determine the cell age, but if you're looking particularly at epigenetics.

[00:35:30]You can look at methylation chains inside these cells and they will tell you basically how old really are your cells.

[00:35:37]And after a certain age in cells, they simply become less powerful because they make more errors in how they function and they have less ability and they are less flexible to adjust to change.

[00:35:52]The key here will be how do you undo these aging changes and there's more and more work that's been done. And as long as you can keep your cells young, there's no age limit. But if your cells are 70 years old, they are not going to repair articular cartilage no matter what you do to them. But if you can somehow revert these cells back into younger cells, which now people are starting to do, then you may have that power and then you may very well be in a situation, maybe not in 5 years, but hopefully in 10, where the 80-year-old, if they have an otherwise reasonable-looking joint may actually be a candidate for cell-based treatments as opposed to today where we really don't have that option.

[00:36:37]>> Yeah, Lindsey, I agree with what Christian said and your question ties into longevity and vitality and all of these things that are very interesting at the moment and very important because in the past 80 years old was old. Now 80 years old is something people expect and they expect to have a great quality of life and we hope to support them in that. But we also know that the hip and knee replacements, which you just mentioned, they do great in 70- and 80-year-olds.

[00:37:02]And there's also people who say they do great in 60- and 50-year-olds, but we also know, honestly, that if you do a hip or knee replacement in a 40-year-old who is an active phase of life and lives his or her life the way they want to, they're going to burn out their hip or their knee sooner than a more sedentary 70- or 80-year-old. So, these novel technologies and these innovations are all aimed at having a successful hip and knee replacement but at a later age because then you will last that that will last longer for you and therefore the next hip or knee replacement that you may need after that will also last longer. So, this will not replace hip and knee replacement in many patient, it will postpone it to where that hip or knee replacement will better fit their lifestyle. And I think the age at which we'll call it middle age is moving and these are therapies for young and young middle-aged patients. They're not therapies for arthritis yet.

[00:37:59]But as we improve our understanding of cellular biology and of aging and of vitality and longevity, we may be able to move that parameter to an older age with better quality of life.

[00:38:10]>> I think that we're uniquely situated in the sense that we represent people that do knee and hip sports procedures but also replacement procedures and understand that there's a population for both. That being said, I think that there's two points to drive home. I think that my even my young patients, but also my 70 and 80-year-old patients getting a hip replacement are very happy.

[00:38:29]But I need to come to terms with fact as of the patient that the day that hip replacement is the best is the day that it goes in. And to that point, there's a secondary aspect of this is that with reclaim, we have gained a deeper understanding of how cartilage can heal itself, how it can be orchestrated to heal itself with stem cells. And I think while reclaim is something that I like to celebrate as something where we have pushed new frontiers and improved patient care.

[00:38:56]Probably the more impactful aspect of reclaim is not reclaim itself, but the insights into cartilage and healing and biology and crosstalk that can unlock then where we're all going to end up in 5 years and 10 years. And that's really that story that we want to continue to be able to be a part of and an active participant in in terms of how can we further things [music] to reclaim 2.0 or whatever great acronym we come up with then in terms of how [music] we can better preserve the joint and maybe one day reverse those signs of aging and epigenetics that Dr. Laderman just talked about.

[00:39:25]>> As you said earlier, a value add. It's a both [music] and. You all make a great team. So Dr. Hevesi, Dr. Saris, Dr. Laderman, cheering you towards victory as you clear your next hurdles [music] in 3 to 5 years. Thank you so much for enlightening us about reclaim.

[00:39:39]Tomorrow's Cure is a production of Mayo Clinic with production help from [music] The Podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcast. And if you liked today's [music] episode, please like and subscribe. I'm Lindsey Siever. Thank you so much for being with us.