Optimizing Physical Performance through Regenerative Therapy and Innovative Technology
January 16, 2025
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Daniel Simon, MD: Hello everyone, this is your Science@UH host Dr. Dan Simon. Today, I am happy to be joined by Dr. James Voos, the Jack and Mary Herrick Distinguished Chair in Orthopedics and Sports Medicine at University Hospitals, the head team physician of the Cleveland Browns, and the University Hospitals Chair of the Department of Orthopedic Surgery and also a professor of Orthopedics at CWRU School of Medicine.
Also joining is Dr. Jake Calcei, Orthopedic Sports Medicine Physician and shoulder surgeon at University Hospitals, and Assistant Professor of Orthopedic Surgery at Case Western.
Welcome to both of you.
Jake Calcei, MD: Thanks for having us.
James Voos, MD: Thank you. Good morning.
Daniel Simon, MD: Sometimes we talk about rare diseases and today we're here with the two of you to talk about something really common, which is osteoarthritis is one example. There are 32 and a half million Americans with osteoarthritis and osteoarthritis of the knee represents the most common form and leads to chronic pain, reduced mobility, disability and impaired quality of life.
And we have the two of you here to talk and learn a little bit about that. So, I guess the first thing that we'll ask before we get into the really exciting part, is what causes osteoarthritis? Why do people get it?
James Voos, MD: I think there's several reasons why people develop arthritis, and the first one is the one that unfortunately, we don't have any control over, which is our parents. Many of us have a genetic predisposition to the wearing down of our joints over time, so there's a familial part from that standpoint. But then there's other things that can occur, such as in the post traumatic setting. If you've had a meniscus injury, or if you've had a prior surgery to your knee that can result in more of a post traumatic osteoarthritis. And then other factors such as obesity or if you have knock knee or bow leg or if you're doing a lot of heavy lifting or long-distance running, all of those things just like the tires on our car can start to wear down the tread, you can start to wear down the cartilage in your knee resulting in arthritis.
Daniel Simon, MD: Great. So, let's start at the easy part. So, Jake, how do you treat osteoarthritis for the person who first comes into the office?
Jake Calcei, MD: So as I talked to patients, a lot of them were active their whole life and spent a lot of time sort of moving and getting those miles on their tires as Dr. Voos described, and I just describe it as getting their money's worth. You know, they get their money's worth out of their joint and getting them moving. So, for me, the early treatments are pretty straightforward, sort of modify some of your activities, work on weight loss, keep your weight down, make sure that you keep your muscles strong, which helps to take the forces off of the joint. Then you can kind of mix in things like maybe an anti-inflammatory medication, possibly injectable options and then really one of the things that helps our patients the most is something along lines of physical therapy, home exercises, trying to get their body in the best shape possible.
Daniel Simon, MD: OK, great. So, we all know we all have family members who've had injections, steroid injections, physical therapy and now, of course, there's a lot of excitement about a very special trial that you guys are doing. As I'm aware the only FDA approved stem cell trial for osteoarthritis. So, James, tell us a little bit about how this got started, your partnerships with people in regenerative medicine, how did this get off the ground?
James Voos, MD: That's a remarkable part about being at an institution such as University Hospitals and having a great partner in Case Western Reserve University that brings scientists and physicians together who may not otherwise collaborate. And this is a perfect example where Dr. Hillard Lazarus and Dr. Stan Gerson as part of the National Center for Regenerative Medicine and part of our Seidman Cancer Center have been growing stem cells for years for blood-based cancers for many different types of blood borne cancers. And so they've had FDA approval and quite a bit of success and experience and we were at a hospital event and happened to be talking in the background and discussed where this would really work if we did this in the musculoskeletal setting, and we have such a great lab here and the level of expertise. So, we sat down and met several times and ultimately put in our application to the FDA and that institutional experience certainly paid off and it took several years, but we were able to get FDA approval to start this trial and injecting patients with mild to moderate arthritis of the knee. So as far as we have seen on our clinical trials registries we're the only institution in the country doing this. So, for us, it's a great example of bringing experts together here in a collaborative institution. It was very supportive. So, we're really excited to have this first phase of the study complete.
Daniel Simon, MD: So, a lot of questions following. Okay, how do you get the stem cells? What are the stem cells? How do they work? Do they grow new cartilage, or do they release magical growth factors and healing factors? Tell us a little bit more.
James Voos, MD: The stem cells are the building blocks in all of our body and most of our stem cells are, we'll use the term pluripotent cells live primarily inside of our bone marrow, but they live in vascular areas all around the body, and those stem cells, what they produce are growth factors that can help decrease inflammation or repair tissue. And then ultimately the cells themselves if they're in the right phase, can move down the line and turn into those mature tissue. And as we think about stem cells today, when you see the billboard on TV or the billboard on the highway, or the advertisement on TV, it’s just taking the stem cells right out of your hip and spinning them down and injecting them right back into the body. And in that case, there's a really low percentage of stem cells. There are growth factors and there are some cells and certainly we've seen therapeutic relief from those, but where this study differs is that very small percentage of stem cells has the capacity to do much more. And what we do in this study is we take those stem cells once we've harvested them into our specialized GMP lab and we grow those cells from the 10s of hundreds of cells into the hundreds of thousands and millions of cells. So we can take that super concentrated stem cell and then all of the good growth factors they produce and inject them back into the body. So I always use the analogy the current way stem cells are done it's like taking a couple drops of lemon juice and dropping it in a barrel of water and calling it lemonade versus when you go to the County Fair and you get the really good concentrated lemonade. That's kind of what we're doing here is we're taking those cells and really amplifying them to magnify their ability to help the body.
Daniel Simon, MD: So, Jake, just from the standpoint of being a patient who's getting this, tell us, so, you inject the cells back into the joint. How many patients have you treated? And based on I know it's early, it's phase one you're escalating the cells, tell us a little bit about the preliminary results from some of your paired MRI's.
Jake Calcei, MD: So far, we have 15 patients that have gone through the trial with both had the aspiration and received the injection. The aspiration happens for us in the operating room. Now this can be done in the office. We take the cells out of your pelvis so out of your iliac crest, we send them to the lab, it takes about two weeks for the lab to purify them, grow them, expand them to a number of about 50 million cells and these are 50 million pure MSCs. And then they come back at the two to three-week mark once the cells are grown, they get an injection into their knee. And the injection just happens in the office like a standard injection that we do like cortisone or PRP-type injection. And after that injection we follow them at standard intervals and what we want to find out is, are they doing more? Are they feeling better? Does their imaging improve? And so, we compare imaging before and after and we also compare their patient reported outcomes or different scores that they give us.
And so, what we found so far is the imaging is improving. So, one of the things that you'll see with arthritis is you get edema in the bone, which is fluid in the bone. It's kind of angry bone, we call it like bone bruising. And that is very painful. And what we found out is that that edema in the bone is going down in follow up MRI's. Patients are doing more, so they're doing things that they haven't done in a while. So they're increasing their activity levels. They're feeling better. So, their pain scores are going down. And overall, the only real thing that we've seen is a little bit of inflammation immediately after the injection that lasts for about a day or so, and yet to imagine there's a lot of activity...we're putting 50 million stem cells into your knee and then after that it calms down and patients do quite well.
Daniel Simon, MD: That's really exciting. So, I think that. Obviously from a phase one, you're going to have to go to some sort of randomized. Tell us about how long you think this is going to be before this will be available for patients on a wider basis.
Jake Calcei, MD: It's a long process for something like this, as it should be, because we want to make sure that we vet things properly and we want to get to a point where we're giving a patient something safe and that it’s going to help them. So, the process is there for a reason. So, we're probably looking at a few years out here. But as we continue to progress this, we'll expand our indications, we'll expand our trial. And that will allow us to include more patients in the trial that will think about the possibility of maybe a second injection, a booster type injection, either six months to a year later, if they're getting benefit from it and really will help us to reach more patients as we continue to grow it.
Daniel Simon, MD: Well, that's very exciting and I certainly look forward to having you back so we can learn a little bit more as this progresses. Well, you know, when you start thinking about these patients, many of them go on to total joint replacement, which is a mechanical solution and your team of course on the leading edge, is saying we should be able to do live joint replacements, let's use tissue. You've developed CollaMedix, which is a collagen scaffold for tendons and now in your collaborations with Dr. Ozan Akkus, after you've received a $48 million grant from ARPA-H to do engineering growth and try to think about this live joint replacement. Tell us a little bit about it and how you're going to build these components to eventually.
James Voos, MD: This is again another example of a remarkable collaboration with Case Western Reserve University and University Hospitals and a great collaboration within our department having partners like Dr. Calcei who are experts in regenerative medicine and are both great clinicians and basic scientists really helped us build a great team to submit and receive this grant from the federal government. And our joint replacements that we do now, as we all know are metal and plastic and it's a remarkable surgery that helps with pain relief and improving people's lives, but there's mileage on those joints and they can just like in an engine, those parts can wear out. And our goal in this procedure is using that same process of being able to capture your cells and grow them into the millions, we can now create a total joint with unique biologic scaffolds. So instead of metal and plastic, these are biologic collagens and materials that can grow into the bone that we can then infuse with your cells, with your own cartilage cells. And then there's one arm where we use your own cells and there's another arm where you can use donor type of cells and ultimately, it's to replace the joints and to resurface the joint with live cells, live cartilage and can we avoid a larger surgery or avoid the metal and plastic in the body? And does that improve people's lives? Does it reduce our need for all the complications that can come with joint replacement? So, we're early in the process, but it's a great multi center collaborative team and we really look forward to our early results. Right now, we are obtaining all of our cartilage samples and finalizing our design, but it's a great team and we're thrilled to be a part of it.
Daniel Simon, MD: So, Jake, you know, ACL repairs are very common these days amongst athletes, especially female athletes in high school, male athletes of all age. It seems like it would be perfect instead of using some other part of the body for their ACL repair, could this CollaMedix material, this scaffold, becomes part of your routine ACL repairs.
Jake Calcei, MD: So, one of the things that is a real challenge for us in sports medicine is the ACL and it's a very common thing you hear about it at the professional level college level and as athletes get more active at a younger age, it's happening younger and younger. It's one of the few surgeries where we actually have to borrow from you to make a new ACL because repairing the ACL, primarily, hasn't had great outcomes. Part of the reason why is because it's an intra articular structure. So, the synovial fluid seems to have some inhibition on the healing of that. And so, what we want to do is to try to find a way that we can repair your ACL primarily without having to borrow from somewhere else, and 1) we think that that will help with the biology of it, right? So, you want to keep your own parts where they belong, and then it also helps in the recovery process because the harvest site is often one of the more painful spots that patients have and can slow down the recovery process. So one of the things that we are working on with our partners over at CollaMedix, which is a Case grown and born company, is to create one of these scaffolds that may help us in the ability to repair the ACL, primarily protect the ACL as it heals and then hopefully improve the biology of patients and potentially get them back to what they want to do sooner. So, the ACL recovery process is long, it's nine months to a year and it's very complicated in terms of the number of resources that go into it from a physical therapy standpoint, athletic trainers, and so, what we want to do is we want to make that process a little easier, we want to get athletes back to what they want to do.
Daniel Simon, MD: Well, that's very exciting. And I think that it's great that we have the two of you and your team leading these because I'm sure everybody would like to preserve what they have and then kind of use their own cells to fix their torn ACL.
So, before we go on to a new topic of sensors. I wanted to just get your thoughts when the last two weeks, a very, very impactful paper was published in New England Journal of Medicine called the Step 9 trial of semiglutide or as we say OZEMPIC or WEGOVEY in patients with knee arthritis, knee osteoarthritis. And there was a dramatic reduction in the WOMAC pain overall score from -41 points with semaglutide to only -27 with placebo. suggesting that this is a disease of obesity, and just as these GLP-1 receptor agonists are really helpful now in kidney disease and heart disease and sleep apnea, it looks like they could be really impactful in osteoarthritis. Tell us about obesity and how you're potentially using and recommending these GLP-1’s in patients with osteoarthritis of the knee or hip.
James Voos, MD: This has been incredibly impactful for us. And you can imagine if someone who may be obese or overweight has developed knee arthritis. One of the things to improve your symptoms is to lose weight, but if your joint hurts, then you can't exercise, and it becomes this negative feedback loop and understandably very concerning and disheartening for many patients when they want to exercise but they can't.
So, this type of treatment, we know arthritis, one of our main risk factors, is that increased load on the joint every time you take a step, three times your body weight goes through your joint. So, if you're on a GLP-1 type of medication and you lose 10 lbs, that's 30 lbs you're saving on your joint every step. So, it is a remarkable thing to improve our pain, to decrease the load on the joints. We also know there's the risk in a joint replacement, surgery goes way up the higher your BMI is, so those patients that have an elevated BMI. If we can get it down and help them lose weight if they do need a joint replacement, the survival of that joint replacement and their risk of complications goes way down. So, I know this is one of those consequences you wouldn't think about with this medication, but it's really helped our orthopedic patients move. Hopefully, it will reduce the prevalence of arthritis within our society just by everyone, again that 10 lbs equals 30 lbs when you're walking, so it's been wonderful for us and wonderful to help as a tool to get our patients moving.
Daniel Simon, MD: That's really terrific and I think it shows you, as you pointed out early on, how important exercises and proper exercise to prevent all sorts of health issues. You know, we know now that probably 4500 to 5000 steps is associated with the reduction in total mortality, cancer incidence, cardiovascular incidence and mortality and obviously very beneficial from your side in keeping you active and keeping your joints and in good shape, so we will encourage that and sometimes they may need a little help with the GLP-1 receptor agonist.
Okay so our last topic for today is going to be this incredible explosion and wearables and wireless technologies for both the professional athletes, the weekend warrior. Tell us a little bit about how you are using and implementing wearables in your sports medicine space to maximize performance and also enhance recovery from injury.
James Voos, MD: The wearable tech devices have really dramatically changed how we train and monitor our athletes after surgery or even while they're out with their team and the usability of the devices, the technology for them to speak real time back to us and the cost has come way down. So, it's allowed us to use it on a larger number of patients.
We were the first team in professional football to monitor our athletes, so we monitored our Cleveland Browns players for two seasons wearing these performance devices, looking at how fast they run, how much they changed direction, what's their workload. And by doing that we were able to predict the risk of soft tissue injury. And so, you can imagine you see on TV, so and so player is out with a hamstring injury, and those several weeks out can make a big difference for that player's life and for their team. So being able to use wearable technology to improve how we work out and now reduce the risk of injury has been remarkable.
Our team also won the NFL Physician Society Research Award. That's the NFL's biggest research award at the NFL Combine several years ago using these same devices, measuring muscle oxygen utilization on our patients after ACL surgery. So, we were able to help our patients recover more efficiently and safer after ACL surgery, using this wearable tech to monitor those internal parameters inside their body, so we're really excited. We've got a very comprehensive program that is testing all of these devices and now we're have different companies coming to us every day wanting us to test and validate their devices and then developing some on our own.
So, it's one of those great things where the level of excitement for us to go from biologics and stem cells all the way over to wearable tech and we've got a really diverse program and it allows us to have that diverse offering to our patients both in the lab and out on the field.
Daniel Simon, MD: Well, that’s really exciting. So, Jake, I'm going to give you the last question here. This is the toughest one. What's the future of sports medicine? Where is this all going? Where do you think in five years? And of course, we're seeing these funky new helmets on the football field. So, I say there's a new helmet, but what's coming down the line in sports medicine?
Jake Calcei, MD: I think what we want to do is we want to keep things safer for the athlete. We want to keep them on the field and so everything that we do focuses on that and whether it's injury prevention or getting them back to what they want to do sooner or prolonging their career. And when I talk to people about what we do with, between biologics, and then we talk about wearables, it seems like a total 180 from each other. And the reality is it's the best way that we can address our athletes and help to take care of them because one, we want to prevent injuries if we can, right? And whether that's having them use the wearables to predict injury, getting them off the field when we need to, keeping things safer, making sure that they don't get too hot when they're working out, things like that, but it may be something as simple as a preventative treatment where we're keeping their joints healthy. Maybe these injections become something that is a maintenance prevention as these joints tend to wear down over time with overuse. And so, I think that the future definitely incorporates both of these realms and one of them is the biologics, and trying to keep what you have and what you were born with and what you've lived with for so long and not just replacing it with metal and plastic or some other part of your body. And then trying to keep you on the field trying to rehab you as fast as we can in a safe manner. And so, these two realms, we kind of mix them together and it's really all for the patient to keep them doing what they want to do and what they love.
Daniel Simon, MD: Well, thank you both so much for joining me today. This has been really terrific. I'm a tennis player and luckily, I guess you'd say my wrist, elbow and shoulder is OK on the left side, but if I need some of these magical MSC's, I know where to go. I will knock on the door. So, thank you so much for joining us.
To learn more about research at University Hospitals, please visit UHhospitals.org/UHresearch.
Thank you, James and Jake.
James Voos, MD & Jake Calcei, MD: Thank you.
Tags: Clinical Research, Research, Sports Medicine