Dr. Zev Nevo Discusses Regenerative Medicine Program at NESS - Nevo Sports and Spine

Hi, I'm Dr. Zev Nivo and I am the founder and medical director of Nestnevo Sports and Spine, which is a medical clinic right here in Sherman Oaks, California. I'm very excited today to talk to you a little bit about one of my passions, which is regenerative medicine. And I'll begin by just telling you a little bit about myself. So I am board certified in physical medicine and rehabilitation. I am fellowship trained in interventional sports medicine, spine and regenerative medicine. I have a board certification from the American Board of Regenerative Medicine and I have advanced certification in musculoskeletal ultrasound. And my interest is really treating people with injuries and conditions, essentially pain conditions involving the musculoskeletal system from head to toe and spine conditions, and provide non surgical alternative options to try to find effective solutions for people dealing with pain. So I wanted to just begin by talking a little bit about the concept of pain. So pain is a subjective symptom that's extreme, experienced by the person who has been dealing with some sort of injury that is experiencing this unwanted and unpleasant symptom. And it, at the end of the day, you know, when you're, when you're dealing with something that's affecting your quality of life that you know can take a tremendous toll on you and to the point where you're seeking medical care. And the important thing is, important question to ask is what are we really seeking here? Are we seeking a solution to address the symptom of pain or are we trying to come up with a diagnosis and a plan for not only addressing the symptom of pain, but why did this happen and how can we prevent this from happening in the future? And I think that's an important concept and really will give you an idea of how we should be addressing pain issues. And, and it really ties in very well with what we're trying to accomplish with regenerative medicine. So as I said, you know, pain as many of you know, can affect, can have an effect in your life where it's affecting some, some sort of movement activity, positional manifestations, where it's, it's causing oftentimes disruptions of sleep, it causes, increases stress, essentially affects the way you're functioning in your personal life, your professional life, etc. And when we look at addressing a problem with pain, we look at more than just addressing the pain symptom, but we want to find out how one's pain has manifested in their life. And we use those goals that the person has as our functional outcomes that's how we will determine whether a procedure or a strategy that we incorporate is successful or not. So ultimately, we also want to understand what has transpired that has caused this pain symptom. And when we're dealing with the musculoskeletal system, we're dealing with soft tissues in the body, Whether it's a joint, whether it's a bony structure, a ligament, a tendon, a muscle. Ultimately there's micro injuries that happen on a daily basis and they don't always manifest in pain. So many times, you know, the body has its own amazing capacity to heal and self regulate. But there are some areas that are notorious that either due to poor mechanics, continue to become re injured and are unable to fully heal. And another major issue is a blood flow issue. So there are some tissues that just frankly don't get adequate blood supply. And the blood supply is a key to how our body heals. The blood actually drives a lot of vital cells, which actually stimulate our own stem cells to try to revitalize and regenerate tissue. So oftentimes it's a combination of this maladaptive stress that we have on an injured structure, combined with the natural lack of optimal blood supply that will cause this persistent pain and dysfunction to remain. So what have been some of the traditional methods of how we've treated pain? So often we try to involves some level of rest, activity, modification, you know, if it hurts, don't do it, that kind of thing. And in many cases, you know, issues will self resolve. But in a large subset of patients, and much of the time, pain conditions can persist. They may or may not be progressive, but they may persist and cause a persistent level of pain and dysfunction. So when you get to the point where just modifying your activities is insufficient, oftentimes there'll be medications that will be recommended, and these fall into the category of things like ibuprofen or even oral steroids. And they are effective in reducing pain in the short term. And the reason for that is because those target the inflammation. They target the inflammatory component which causes pain. And while that may sound like a really good thing, the issue is that the body inflames for a reason. Inflammation, which involves redness and swelling and pain, is actually a necessary component, a necessary way of how our body communicates with us that a problem has taken place, that an injury has taken place. And it's our body's way of telling us, hey, you know, don't put so much pressure on this area because we're trying to heal secondarily. The swelling will actually drive that blood flow. So, so that's the way the body attempts to heal. The issue is that when there is an incomplete healing that takes place, you're left with this ongoing kind of low level inflammatory process, which is what we believe occurs in conditions like osteoarthritis, for example. So then you get to a point where often considerations are for injection based treatments. Obviously, physical therapy is something which will be tried early and often, but sometimes when the pain is too severe, you know, it's hard to fully engage in the therapy and really find optimal improvements. So sometimes we need to go towards injections. And then the question is, how are the injections done? Are they done with the use of an ultrasound or do you have very specific diagnosis? And furthermore, what are we actually injecting? And traditionally, for many, many decades, the injection of choice for many pain conditions are steroids that are given in an injectable form. And you know, many studies, when they look at head to head, you know, steroids versus placebo, or even some of the regenerative treatments versus steroids, in the very short term, steroids are still effective. But what are they effective in? They're effective in relieving pain, but the long term functional outcomes are not that great. And as we know through many studies, is that steroids actually will cause further degradation of tissues and joints and will actually get someone to progress to requiring surgery potentially even sooner. And it really does nothing to improve the microenvironment of the tissue itself. So if pain is kind of the only goal, then steroids are still a viable option. But there are other systemic side effects to think about. Those who suffer from diabetes can have alterations in their sugar, it can cause irritability, it can cause osteoporosis, it can cause some hormonal effects in the long term. So the trend right now and the paradigm shift in medicine in musculoskeletal medicine is really to try to shy away from encouraging anti inflammatory based medications, whether they're topical, oral, or injectable. So outside of surgery, where does that really leave us? And that's where regenerative medicine comes in. So first, just a little bit of a disclaimer. The field of regenerative medicine is vast. It spans multiple specialties, even beyond, you know, the orthobiologic use, which is the use for orthopedic conditions. And the evidence varies quite a bit. And it really depends. It's really important to understand what is being recommended as part of a regenerative medicine strategy. And I'm going To focus very briefly on just two of the most studied uses of regenerative based therapies, which include something called prp, which stands for platelet rich plasma, and something which colloquially is known as a stem cell procedure, which I'll clarify, which is a bone marrow Asperger concentrate, also known as bmac. And just to define the goal, what is our aim with regenerative medicine? Why is this different than a steroid injection? And the reason why I went into so much detail about how injuries occur and kind of what's going on under the surface is that actually the aim of regenerative treatments are not just to improve pain, but actually to have an effect on the micro environment of the tissue that's injured, as well as trying to harness the body's own system, cells that naturally heal when we have these micro injuries or even wounds, and use those cells to try to create a robust response locally at an area that has been affected by injury. So that's the beauty behind it, is that we're trying to accomplish more than just pain reduction, but as opposed to certain therapeutics which are meant to extrinsically kind of help us on a macro scale improve our function, we're trying to actually improve the function and integrity of the injured tissue. So important to understand is also something that I'm very passionate about, which is the use of technology to actually make us more accurate and effective in our treatments, and that is with ultrasound. So ultrasound is another whole topic, but essentially what it affords us is a very easy way to make specific diagnoses, but also use ultrasound for needle guidance when we do injections to target a very specific structure that's injured, to put the stuff where it needs to go and nowhere else. There's also improved safety where we can avoid structures. So for example, if we're treating a tendon, we want to avoid nerves and arteries and veins that we don't necessarily want to puncture or, you know, involve. We can very carefully guide our needle around and away from these structures. And it also creates an environment where the patient experience is improved, so they're typically more comfortable. Especially if we're about to get near a sensitive area. We can provide adequate warning and patients can also, you know, watch the procedures live. And then the last part is the concept of what we do after the injection. So contrary to popular belief, or maybe it's not popular belief, the injection is not the whole thing. Right. So there needs to be a plan in mind. So what I like to do when I evaluate these conditions with patients is Come up with a short term and a long term plan. And typically this is what we utilize when we come up with a regenerative treatment strategy in that after the injection to set expectations that this may take some time to take effect, that it will take buy in from patients in terms of the to do's and the not to do's to try to promote the most effective and efficient healing response. And together with that, we're engaging the patient on their own as well as with a therapist in something called regenerative rehabilitation. And this is a new area within regenerative medicine where we're incorporating concepts that we know, long standing concepts of physical therapy, where we're using something called mechanotransduction, we're applying forces very specifically into injured tissues to try to actually have the injectate the cells that were injected, be more effective and actually turn into the cells that we want them to. And I'll go into a little bit more detail about that. So let's talk a little bit about prp. So PRP is known as platelet rich plasma. And what we're doing is that we're getting a sample blood from a vein, typically in the arm. And when we extract, like when you have a blood draw, when you extract whole blood, as it's called, or venous blood, there are three main components. There's the red blood cells, the white blood cells, and then the platelets and the plasma watery layer. And the red blood cells we know are important to drive oxygen to our tissues. However, they are not our friends when it comes to injured tissues. So if one is bleeding into a joint or bleeding into an injured hematoma in a muscle, for example, that can be very inflammatory and painful. White blood cells are very important actually for driving immune response. And the platelets are kind of one of my mentors described as nanorobots. So they're very well known for being involved in kind of clot, the clotting cascade and also becoming very sticky when they become activated. And this is really what we're going for. So what we do in a PRP procedure is that from a sample of blood, we use a centrifuge machine to spin the blood and separate those various components by different densities or weights. And what we're trying to extract is primarily the platelet component diluted with some of the plasma or the watery layer. And the benefit to that is that along with the platelets themselves, which when they're placed in an area that has injury, become activated, as I said, and what happens is they tend to become very sticky. So they seal up gaps or tears in the tissue very well. They become almost like a scaffold. And they also hold in place their most component, which is these granules that are within the platelets. And there are various types of granules. But the focus in terms of regenerative benefits involve the granules called the alpha granules. The alpha granules are packed, jam packed, like packed water balloons filled with hundreds actually, but several dozen of which are extremely important growth factors and cytokines and proteins, which are very involved in healing and in wound healing. And those are what we're going after. So when platelets are injected, when a platelet rich plasma, which is a concentration of platelets above your normal level, and we've gotten rid of the other portions of the blood, when they're injected into a site of injury, they immediately become activated and the granules release their contents. About 70% or so is released within minutes, and then the remainder is released over the first few days. And this first phase of about a week we call the inflammatory phase. So actually there may be a little bit of increase in pain and discomfort over that first week because we're trying to recreate, we're trying to not necessarily trick your body, but actually recreate the process of healing and recovery and as those. So this is kind of the time to talk, to talk about the phases of healing. So the three phases are the inflammatory phase, which is kind of that first week and what that is, we're really just trying to kind of shock the body into addressing this area once again, especially if this has been a chronic issue that hasn't been improving or resolving for quite a while. The second phase, which begins around week one and two, is called a proliferative phase phase or the proliferation phase. And the proliferation phase, I like to give the analogy, I like analogies. So the analogy I like to give is kind of like you want to bake this complex cake. And in order to do so, you know, it's not like you have a show where everything is kind of already separated and measured. You have to go and purchase all the ingredients. So that's essentially what's happening in the proliferation phase, is your body has this system signals from the contents of the granules that are now calling on all the processes that need to take place in order to start to, for example, lay down new collagen fibers. So collagen is like flour. It can be used, it's the components that are used to form various types of tissues. And we're Kind of accumulating all of these that are necessary to repair. Finally, after several weeks, you get into the remodeling phase, and this phase will actually last for months. The remodeling phase is actually where some of that immature kind of wet cement begins to form. Much more mature and much more strong and resilient tissue, which is closer to the original tissue that, you know, young, vibrant, healthy tissue that we're aiming for. However, in order for all of this to occur, first of all, it's not black and white. So there's always going to be a range in terms of recovery, in terms of how quickly things advance. But what we found is that if you incorporate certain elements of physical therapy, a progressive program like we use with athletes who are on a return to play, we try to get them at a high level of function. We want to start with addressing pain initially. Then we want to maximize range of motion. Then we want to work on strengthening. And there are various types of how you can strengthen injured tissue. And finally, we advance to things like neuromuscular re education and basically teaching your body to function at a higher level where you can do movements in multiple planes and basically put a lot more stress and demand and resistance on your joints and tissues where your body is already set up to be, be able to kind of handle that. So the idea that I want to drive home is that that first inflammatory phase is actually about modulating or controlling inflammation. And that's what our aim is to do. So inflammation is not bad unless it's out of control. But the benefits to our a lot of regenerative treatments is the balance act where you have the right amount of inflammation. Furthermore, we like to refer to PRP as an indirect regenerative treatment as opposed to direct. And the reason for that is because PRP does not really contain any stem cells in them. And that's kind of what separates it from a bone marrow aspirate concentrate procedure. So the bmac, or bone marrow aspirate concentration procedure, contains very similar contents like the PRP does. However, it also contains two types of stem cells called MSCs or mesenchymal stem cells, and HSCs, which is hematopoietic stem cells. Now, those aren't the types of dangerous stem cells that are cancer forming because they are what's called multipotent as opposed to pluripotent. So the multipotent stem cells can only form a certain lineage of within the mscs, within the mesenchyme. So it forms kind of connective tissue like structures like bone or Fat or blood or tendon or ligament or muscle, et cetera. Hematopoietic stem cells are blood forming cells and they actually work in concert with the mscs to create a very robust response when they're injected, similar to the PRP at the site of injuring. And just one note on the use of stem cells. The original hope was that injecting these stem cells will actually help to regrow tissue directly by the cells we're injecting. But we now know that to not be the case. So it's a little bit of a misnomer to call it a stem cell procedure. And actually Dr. Kaplan, who actually coined the term mesenchymal stem cell, recently renamed it more appropriately a medicinal, medicinal signaling cell, because that's how we believe the process to work now is that what we're doing is we're really controlling the micro environment of the tissue. So when the stem cells are placed in there from the bone marrow, they are stimulating very strongly your own stem cells to work in concert with the growth factors that are released. And the major difference with the bone marrow procedure is that there's an additional harvesting which is done also with ultrasound guidance at the back of the hip where we extract stem cells out. And then there's a similar preparation process through a centrifuge to try to concentrate the cells that we want. So one interesting point in terms of evidence is that a recent study out of France looked at patients who required bilateral knee replacements. So their knees were that bad on both sides that both of them were eligible for surgery. And what they did was they, they did surgery on one side and they did a bone marrow procedure on the other side. And what's interesting, after about two decades of follow up, they found that there was almost equal amounts of necessity for another knee replacement surgery, whether they, whether it was on the side that had the knee replacement initially or it was the side that had the bone marrow stem cell procedure. So there is a lot of evidence out there specifically on joints. But the. But it has expanded especially over the last decade when it comes to prp, especially to involve conditions head to toe. And I am amazed by the utilization that I'm seeing, seeing where it's being replaced for things like epidural steroid injections in the spine, it's used for neuropathy, carpal tunnel syndrome. I don't believe it's a cure all, but it's. I think it's important to have a conversation to see if it is an option and if one is a good candidate, because I think it is the future and it definitely can and should replace steroids for the most part part as an injection based treatment and when one is kind of concerned about improving the function of their tissues. So last but not least, I want to just briefly talk about what happens after the injection. So I talked about the importance of physical therapy and I think that as a side note, physical therapy really plays a tremendous role, not only when one is in pain, but even after one is recovered. The purpose is that we're trying to train the body to be equipped to handle different types of activities and be stronger than what you're trying to put your body through. Don't be defensive about your pain. So in times when things are better, we want to recommend a maintenance program. But some of the techniques that we use in physical therapy are vital when we're trying to recover from a regenerative procedure. That's why our protocols are. We took protocols that were initially made for, you know, high level athletes and what we've done was made it more practical for the everyday hard working person. And regardless of your 15 or 95, if you're working or retired, whatever it is that has been impacted by your pain, we look at those as the goals for return to play. That is your return to play. And that's what we look at when we're building this protocol for you. So what we do is we actually will have a calendar where we follow the timelines of wound healing and we create both a home exercise program and a therapist guided program to work with you through these phases with frequent follow up. So we can make sure that we're getting you where we need to go. And just something for the future that's interesting is that we're looking at using other ways of stressing the tissues, not only through physical therapy, but by using modalities like shockwave therapy to actually improve the outcomes and get people better faster.