Lessons in Orthopaedic Leadership: An AOA Podcast
Lessons in Orthopaedic Leadership: An AOA Podcast
Groundbreaking Advances in Regenerative Joint Treatments with James L. Cook, DVM, PhD, OTSC
Unlock the future of orthopaedic surgery with our enlightening conversation featuring James L. Cook, DVM, PhD, OTSC, a pioneering expert in regenerative orthopaedics. Learn about the transformative potential of cutting-edge treatments, including the innovative combination of Hyaluronic Acid (HA) and Platelet-Rich Plasma (PRP) for joint health. Dr. Cook sheds light on the importance of evidence-based practices, regulatory challenges with mesenchymal stem cells, and the perils of unverified "stem cell" treatments. We emphasize the need for clear guidelines and insurance coverage to responsibly advance this promising field, ensuring patient safety and efficacy.
Discover the groundbreaking advancements in biologic joint regeneration, from the promising results of PRP and Bone Marrow Aspirate Concentrate (BMAC) to the future of biological grafts and tissue-engineered solutions. Dr. Cook discusses the necessity of standardization for consistent outcomes and highlights the crucial role of comprehensive care centers. We also delve into the financial considerations and insurance hurdles that patients face, stressing the importance of integrating these innovative treatments into mainstream orthopaedic care. Join us for an insightful exploration of how regenerative orthopaedics is poised to revolutionize patient care and the future of orthopaedic surgery.
Welcome to the AOA Future in Orthopedic Surgery podcast series. This AOA podcast series will focus on the future in orthopedic surgery and the impact on leaders in our profession. These podcasts will focus on the vast spectrum of change that will occur as the future reveals itself. We will consider changes as they occur in the domains of culture, employment, technology, scope of practice, compensation and other areas. My name is Doug Lundy, host for this podcast series. Joining us today is Dr Jimmy Cook.
Speaker 2:Jimmy Cook is a board-certified veterinarian. He also has his PhD and is the director of the Thompson Laboratory for Regenerative Orthopedics and the director of operations and research at the Mizzou Bio Center and the William C and Catherine E Allen Distinguished Chair in Orthopedic Surgery at the University of Missouri. As I said, he's board certified by the American College of Veterinary Surgeons and the American College of Veterinary, sports Medicine and Rehabilitation. He trained at the University of Minnesota and the University of Missouri. His research interests are focused on in vitro and in vivo models, tissue engineering, osteoarthritis, meniscal replacement and regeneration, articular cartilage, as well as other areas. I had the pleasure of meeting Dr Cook at the Southeastern Orthopedic Symposium run by Dr Jim Standard, and I was immediately blown away by Jimmy's incredible knowledge of regenerative orthopedics, of PRP, bmac, of all that stuff that's out there and the true nature of it. So, dr Cook, sir, welcome to the podcast series.
Speaker 3:Thanks so much for having me, Jimmy.
Speaker 2:you are also one of the nicest folks I've ever run into. Thank, sir, welcome to the podcast series. Thanks so much for having me, Jimmy. You are also one of the nicest folks I've ever run into. Thank you so much for all the work that you do for our patients and all the understanding on this. Can you just give the audience just a overview of what your work is, what your background is and how you got into this?
Speaker 3:Well, you gave a great intro, thanks. I mean, I kind of came from the veterinary world and then went over to now. What I say is work on the two-leggers full-time. And so, as you mentioned, jim Standard, a great friend of both of ours and my chair, and just a wonderful clinician, scientist and human being, brought me over here as we were kind of developing this area, to be honest with you. So both in the osteochondral transplant and meniscal transplant area of regenerative orthopedics, but also in the orthobiologics, and so we really wanted to bring those forward in an evidence-based way. Certainly, we wanted to look at discovery and groundbreaking cutting edge, but do it in a really thoughtful and, again, evidence-based way.
Speaker 2:So can you give us an overlay of what the current state is in the United States? For, however you would define, I'm not going to put any any parentheses on it. I'll let you figure out. You define for us what regenerative orthopedics is. What does that mean in the US and what are the current players in that?
Speaker 3:Actually I think you said it and we're still in the defining stage, right. So I would say it's the frontier stage which is good and bad. I mean, it's fun to be on the frontier and you know we can explore new directions. But there's limited guardrails, and I think you know, especially when we talk about patient safety in combination with efficacy and I always say it's what we're trying to figure out is what we can do, what we should do and what we shouldn't do, and I think that's really where we're at.
Speaker 3:So again, I mean, the FDA guidelines for what we can use as indications are even not super specific. They're these general kind of minimally manipulated, not combined with other substances, homologous use, administered during the same procedures, collection. But that's a little tough too, and so again, I think it's really our responsibility, you know, to define that for ourselves and base that on the patient, base that on best current evidence. But then that's also going to help us in the long run, because the other, I think, difficult thing about the frontier era of this is it's hard to get insurance coverage right and you don't want to just cash pay, cash pay, cash pay. Number one, if it's not worth it, cost effective, but number two we're never going to get insurance coverage if we don't kind of demand that based on the evidence.
Speaker 2:So we're talking about stem cells here, right?
Speaker 3:Yeah, my favorite. So honestly, for me that's one thing.
Speaker 3:If you use the terminology correctly. That is actually clear. So true stem cells cannot be used and without IRB approval for a special indication in orthopedics today and a lot of people, I think even orthopedic surgeons are going to say like what, everybody's using them, they're on all the billboards and all the advertisements. I see patients every week that paid X thousands of dollars for stem cells. But those are and we have to use the air quotes here. Those are stem cells in quotation and they're not really that.
Speaker 3:And the problem is I think we get confused of you know what basic science or even translational science tells us about true mesenchymal stem cells, which are very powerful little cells and can kind of do all the things that we hope to. But again, based on current FDA regulations, we can't use those. But again, based on current FDA regulations, we can't use those. It's actually illegal to use mesingual stem cells in clinics today without some specific IRB approval. And so the stem cells that people are using, again in the air quotes, don't have that robust evidence and a lot of times they don't work. And I think you know not to scare anybody or be, you know, too hyperbolic here, but you know we've definitely seen some safety issues with the stem cells in quotation.
Speaker 3:So, yeah, we focus on all the other ones that are much more clear, I think, in terms of a legal, appropriate pathway, with some evidence-based indications in level one and two studies that can safely help people if used as we should, not as we just can.
Speaker 2:Right, right. And I love when folks come in saying, well, I had stem cells, and I'm like, wow, in the US, and they go, yeah, I go, that's against the law. Actually, does the Food and Drug Administration know about that? And their eyes get as big as saucers and what they really meant was, you know, was PRP, or something like that. Speaking of which, as you see it, what's the current stand for PRP?
Speaker 3:if you want to throw BMEC in there as well, yeah, I mean that's definitely what we're using mostly in this area of regenerative medicine. Orthobiologics is PRP. I think it definitely has robust evidence, especially in certain indications. I mean, I think, for mild to moderate osteoarthritis.
Speaker 3:We can be very confident in leuko-reduced platelet-rich plasma, autogenous platelet-rich plasma, as you know, being 70 plus percent likely to have good pain mitigation and functional improvements in patients, at least with knee osteoarthritis. And I think we can we can expand that to some of the other joints. You know get about a 75, 70, 75% successful response rate if you will, for about six to nine months, I think. Safety equivalent to placebo, so it's very safe. It's one thing I love about PRP super safe. And then efficacy. I think you know in level one studies more robust efficacy than hyaluronic acid alone, and so that's definitely what.
Speaker 3:I, if somebody says what is the evidence, kind of like you just asked me, that's what I would say from there, I think the other indications are increasing. So we use it a lot PRP for tendon hamstring epicondylitis, you know those other indications where we can jumpstart the healing process, try to speed up the healing process. But also, then, what's cool about PRP, right, is it's this biological soup, and that's what I. You know, one thing you've heard me say before and I try to always add in these conversations, is we're never smarter than God. And so I think you know, trying to give a super physiologic dose of one thing like back to you know BMP or even HA, you know those are basically super physiologic doses of one component of an incredibly complex healing joint health metabolism process.
Speaker 3:So what's cool about PRP is it's way more than that. Right, it's a soup of kind of physiological during the healing process 1500 different proteins in every little platelet. And what's cool for us as orthopedic surgeons is a lot of them are geared toward musculoskeletal health and healing anti-inflammatory, anti-nosusceptive, anti-degradative, you know. And so just along with them, the growth factors and the things that stimulate healing. And so it's just cool, it's cool to think about and it's cool to try and harness that for the benefit of the patient.
Speaker 2:Very good, that's a great overview on PRP. What else is out there besides PRP that's in your mind is currently cool, acceptable, safe and effective in 2024?
Speaker 3:introduced, except for a chronic degenerative process. Because I think you know, we all know, we hopefully remember from our physiology classes that you have to have inflammation to get something to heal and so it's just the right type of inflammation at the right time. And these degenerative processes, chronic ones inflammation process has actually failed to jumpstart the healing process and so we kind of restarted in those. So again, usually like a degenerative Achilles, you know, maybe where there's some calcification around a tendon or calcification within the muscle, we might switch to the leuko rich, so white blood cell high, containing PRP, to again stimulate that process and use all the other parts of PRP to try to get that going. For me it's easy to then kind of get the algorithm so Lugaridus, prp for everything except degenerative processes, except when the indication has the word bone in it. So if the indication has the word bone in it so tendon to bone healing, non-union fractures, stress fractures, for us the osteochondral allograft transplantation where we're trying to get osteointegration, as soon as you say bone is the primary thing in the indication, then we switch to bone marrow aspect concentrate, so BMAC. So again, at least for us it's a simple algorithm that we go through that way and the cool thing about that is then you can really use the indications for label which also then means insurance coverage pretty effectively in those ways.
Speaker 3:The only other thing that we're doing quite honestly in this arena is we are sometimes combining HA with PRP in the joint. I would say there's burgeoning emerging evidence for that coming on. It does make sense to me scientifically because HA is one lubricant, right, that has some other properties, but it's really. Ha is really mostly for cartilage on soft tissue lubrication in the joint. Superficial zone. Protein or lubricant is for the cartilage on cartilage lubrication and what's cool about that is PRP has a bunch of that in.
Speaker 3:So if we take advantage of the HA, which PRP does not have, combine it with all the great parts, including superficial zone protein, lubricin and PRP, then maybe we're even accentuating the PRP to the maximal level Safe and effective. The biggest thing there, I think, is it's a bigger injection and probably insurance is only going to cover the HA. So you're going to have to go back to the self-pay part for PRP, even if they would have covered it for something else. So that's the only, I think, thing we have to navigate when we're trying to combine those. But in terms of safety and efficacy. We've been really happy with that one navigate when we're trying to combine those. But in terms of safety, and efficacy we've been really happy with that one.
Speaker 3:You know I'm definitely keeping an eye on things like Amnion, but I just, you know, haven't seen the evidence yet and I'm just not sure that when you break it down to its components, at least for in the joint and the primary musculoskeletal indications that we typically talk about or reach for, or regenerative orthopedics or biologics, I'm just not sure the components are really geared toward that.
Speaker 3:You know, it's definitely not as diverse of a composition as PRP and it's really, you know, more of a, I guess, early process developmental. I mean, that's where it is right, it's in the, it's in utero or in the placenta, and so, you know, I just think it's kind of geared toward a different thing. I mean, that's why I would say, is it? You know it's kind of funny we talk about this topic, because I think, you know, really regeneration is pretty impossible once you're an adult, you know. So what we're trying to think about is more effective repair, better remodeling, better tissue health, and so, again, that's where I think, coming back to the things like BMAC and PRP, where it's geared toward healing tissues that have been damaged, rather than developmental biology, if you will, it just makes more sense to me in a real world orthopedic practice.
Speaker 2:So that's very interesting. So you touched on the amniotics. Others like adipose. There's a lot of other players in the mix. Any thoughts on any of that more fringy kind of restorative stuff that's out there now?
Speaker 3:I really think those are all and this is opinion but it's based on lack of evidence, I would say so everything I've tried to say up until this point was based on evidence, clear evidence. Now I'm saying opinion based on lack of evidence and that always scares me because it's being used so so much. But I think you know adipose derived stem cells, again in quotations. Even bone marrow derived stem cells, again in quotations, even bone marrow derived stem cells, again in quotations For the indications that we're talking about. I just have not seen the evidence and we totally avoid them Because the other reason is, I mean, without that evidence they're all way more expensive and zero covered by insurance for orthopedic indications, zero covered by insurance for orthopedic indications.
Speaker 3:So here let's just compare it straight up, right PRP, you know, I mean probably the most I've seen for a single injection around the country is around $1,200. Cash pay here it's honestly the PRP part is $250 for a single injection. So even if you have that range and then you compare that to what even in town here in Columbia, missouri, or what I've seen across the country, is more like about 1800 to I've seen for a single injection advertised $11,000 for adipose or bone marrow drive, stem cells and quotations. And then about 50% of our PRPs are covered by insurance now for knee osteoarthritis and 0% across the US are covered for stem cells by insurance. Stem cells and quotation by insurance. I mean it just seems pretty clear, right Like you just stack up those comparators and you say, why would I do that? Especially when, then, the efficacy evidence is completely in favor of PRP or BMAC.
Speaker 2:I've got friends who unfortunately have got pretty significant metastatic cancer and the oncologist here in the US have basically said you know you're now in palliative care and they don't want to give up yet.
Speaker 2:So they have taken their life's resources and gone to certain countries outside the U? S and paid for incredible treatments and I'll put air quotes on those that to date every one of those friends of mine have had no benefit to their cancerous and have died from it, unfortunately. But I've also been aware of patients who have left the country in search of restorative biologics and stuff. Any thoughts on where that's the status of that is out there currently?
Speaker 2:in terms of outside of the United States, outside of the developed probably the developed world, you know, developed Europe and such and other places where we should be a little wary.
Speaker 3:Yeah, that's it. I mean, be wary for sure. You know, the really frustrating part to me about this whole thing is true mesenchymal stem cells can have amazing effects honestly, probably truly regenerative effects in some applications and indications, when used correctly and safely, and all that.
Speaker 3:So I don't want to throw those out and I think again every time I just probably a nauseam, just say like we really got to be careful of semantics because, everything that we're using in the us and unfortunately a lot of those other ones are the who knows what, the stem cells and quotations and and potentially very dangerous if and when and in some indications, when we or other places in the world can use true mesenchymal stem cells that are shown to be that and you have to show that by a bunch of different scientific tests to say they're true mesenchymal stem cells in some indications you I think that can work. I'll be honest with you. You know I'd be hypocritical if I wasn't saying this because fortunately we're just part of a big ARPA-H grant that is using stem cells to tissue engineer whole joint replacement. It's a moonshot. I don't know if we'll get there, but I mean it's possible. And wouldn't that be amazing if we're able to do that and truly regenerate a whole joint or parts of a joint, that could really move the pendulum, move the needle in terms, under the careful microscope no pun intended of regulatory bodies that are going to say like safety first, man, I mean, and especially, if nothing else, safety for your checkbook, right? I mean we've had people come to us that have spent over $100,000 on stem cell injections or other regenerative treatments, including in other countries like you've talked about and again, not only no benefit but some of them had, you know, inflammatory arthritis, immune mediated problems from that, septic joints.
Speaker 3:So it's just, it's, it's, it's again, it's just got. We got to be super careful with it. And I think you know, I don't know of any place that I could say safely, does true, inside of this country, outside of this country, you know, does that safely at this time point where I would say like, yeah, it's worth a try If you're at that point like I'm going to lose my leg, I'm going to lose my joint, I'm going to, you know, die of cancer. I still don't know of somewhere where it's regulated enough but cutting edge enough to say that compassionate humanitarian care is worth it, if you will.
Speaker 2:Right, right, that'd be crazy if y'all could get entire joint replacement just from not just from, but from these restorative methods. All right, which leads us to the next part. Where do you see this going? And you could pick your future timeline, whatever you'd like it to be 5, 10, whatever years ahead. Even further, what will this look like in your and Jimmy Cook's mind out there in the future, in terms of just the direction you see, of how we'll end up?
Speaker 3:Yeah, I think I see two ways. I mean one is, I think, just expanding this current one, because again, I do think we have great arrows in the quiver. I think PRP and BMAC are great arrows in the quiver if you use them well. So I just like to get those arrows clear and indication so people are speaking the same language, like when we say I gave a PRp injection, what does that mean? So we can compare apples to apples in different studies. And then you know, also along with that is just get like insurance companies. It honestly kills me and I don't. I do get it because it's so complicated, but at the same time I don't because prp has level one evidence meta-analyses that is better than ha, but insurance companies will still pay for HA, which is more expensive, and not PRP. So I just say like, let's just get it pragmatic and practical for the patient, like, and it still benefits the insurance companies, right. So let's just get that where we're using the same thing, we're talking about it in the same way and we're getting it paid for to help patients, which will move that part. I think that will move that area vastly far forward, because then we can do those studies, those registries that really say like when does it work, when does it not work, what's can, should and shouldn't in this frontier, and then we move off the frontier. We just know what we're doing for patients.
Speaker 3:The other part then is a the really, you know, moonshot pie in the sky, holy grail part, which is regenerating joints.
Speaker 3:So I think, biological whether those are allografts, you know, of different types, or truly tissue engineered regenerative medicine I mean I think it's cool that ARPA has, you know, put the money into saying like this is crazy.
Speaker 3:I'm like it's going to be the coolest thing in the world if we can do this, but let's give it a try, because we're going to learn stuff and we're going to move something forward. You know, I mean you know better than I do that metal and plastic are awesome for the right patient. I mean there's so, so, so many people that are happy with their artificial joints and there's so, so many people that aren't, that want something different, right, and so I think if we can just dial that in and have something that truly could be regenerative or at least as joint preserving, restorative as possible to return function in these young patients you know that the average age for artificial joint replacement is going down, which is a little bit scary, and so trying to get those two avenues going, I mean that's my dream. My dream would be that you know biologics are part of a comprehensive care center in every orthopedic institution and everybody knows what can and can't be done and what should and shouldn't be done.
Speaker 2:In both of those realms- it's interesting because part of what you're also talking about on the payer side is there's a move, especially out of certain places like Texas and Nashville, about moving off of procedural-based bundles and onto diagnostic-based bundles. So you could easily see in the future that this restorative medicine would be part of a knee pain bundle where the 70-year-old with the destroyed knee goes on to total knee arthroplasty and a 45-year-old with a big MFC injury could enter the restorative side.
Speaker 3:Yes, yeah, I mean I would love that. I mean that's exactly what I envision I think is the right thing, right, I mean that's what? And just those options that patients and you know healthcare professionals understand what the options are and how they would be cost and efficacy. Effective, value-based, truly value-based right Care moving forward.
Speaker 2:Anything on meniscal transplants. I know you work on that as well. Anything, you see where that's going.
Speaker 3:I mean, that's part of it for me. I think we've really shifted toward viable, so fresh meniscus transplants, and our early results are showing that. So again, the same kind of thing like truly biologic, not just a dead piece of tissue that can serve a biomechanical function, which can be, good, of course, but the truly biological part.
Speaker 3:You know I always say that biology and biomechanics are inextricably linked in orthopedics and you really can't have overall success without kind of combining those and augmenting those together. And so that's really what we've tried to do, is take it to the next level, truly make it a biological meniscus transplant and a biological cartilage transplant and hopefully let those donor cells do their thing in the body and kind of keep it longer term and more truly functional in the joint.
Speaker 2:Any other futures and regenerative stuff that you're thinking of?
Speaker 3:The only other thing I would say is I would like to see like you were talking about is the truly cutting edge stuff, but under a safety net. So you know if we can, if we can say this is high risk, but you're fully informed, you know it's maybe a humanitarian situation, whether it's loss of life or limb or loss of quality of life Right, and say like, with all that fully informed, under the guise of at least safety, you're taking more of a risk on efficacy. You know, let's, let's try that in a center that's geared toward this, that's going to do the comprehensive patient care that gives you the best chance for that. I would love to see that. I mean it's difficult and risky. You know both medical, legally you know, and just advocacy wise. But I think, if done right, you know, like some of those, I think about things like the Center for the Intrepid Right. You know that's trying crazy stuff to save our amazing veterans and service members' life and limb. It would be cool to do that in this area as well.
Speaker 2:Wow, it's been once again an absolute pleasure to discuss restorative regenerative biologics and surgery with Dr Jimmy Cook, who is the director of the Thompson Laboratory for Regenerative Orthopedics at Mizzou, working alongside all the great orthopedic surgeons out there at Missouri and trying to find the restorative ways and the best ways for us to use these new and interesting biologics coming down the pike and, if you haven't heard it already, Jimmy knows more about this stuff than anybody I know. So, Dr Cook, thank you once again so much for being on the AOA podcast.
Speaker 3:Thank you, it was really fun and I learned a lot too, so thanks.
Speaker 2:Thanks, Jimmy, All right y'all and stay tuned for more futures in orthopedic surgery in the podcast series by the AOA. Thank you.