Good evening, everybody. I first want to thank all of those who have attended tonight. My name is Shannon Strader and I'm a PGY2 at the University of Louisville and this year's RFC research representative. I'm very excited to be continuing the AAP and AR3T Orthobiologics and Regen Med series. The goal for the webinar series is to provide comprehensive education for physicians in training and physiatrists interested in regenerative rehabilitation while reducing stigma, misinformation, and encouraging responsible advancements for the regenerative field. AR3T is now offering a certificate of attendance for those who attend eight out of 11 offered webinars this year. You must register at the AR3T link I'll put in the chat box later tonight and ask one question in the chat box during each webinar that you attend. If you do have a question this evening, please write it in the chat box during the webinar and we'll go over as many as time permits. All right, it gives me great pleasure in introducing our brilliant speaker, Dr. Master. Dr. Zubin Master is an associate professor at Mayo Clinic's Biomedical Ethics Research Program and the Center for Regenerative Medicine. Previously, he was an associate professor at Albany Medical College and a senior policy advisor at Health Canada. He completed his PhD in biomedical research at the University of Toronto and postdoctoral fellowships in bioethics and health policy at Dalhousie University and the University of British Columbia. Dr. Master serves on several scientific committees and editorial boards and has held several adjunct or visiting professor's appointments. His research examines ethical and policy issues related to stem cells and regenerative medicine, genetics, and research ethics. Thank you so much for teaching us tonight, Dr. Master. Thank you, Shannon, for that warm introduction. I don't think anybody's ever said such nice things about me. Yeah. So thank you. Okay. So hi, everyone. So I'm looking at the number of people. So I'm pretty informal. I'm kind of monitoring the chat, but I may not really pay attention. If you do want to ask me a question or something, I'd be more than happy to answer it, you know, sort of in the middle I've saved quite a bit of time at the end to, you know, chat with you about whatever you'd like. Okay. So let me begin. All right. So just to declare, I don't have any conflicts of interest in terms of having any payments from product manufacturers or distributors. I'm not going to be talking about specific products or anything like that. I should just declare that I am a member of the International Society for Stem Cell Research. I'm one of their Goldstein science policy fellows and member of their education committee. And as a Goldstein fellow, I'm also an ex officio for their public policy committee. And I will make some one reference or two references to ISSCR. So why do I think this is important? Well, whether you're a basic scientist or if you're a clinician of any sort working in physiatry, in sports medicine, potentially even in some type of an ortho practice, I think it's really important for you to know this because you either will be talking to patients and or the public. And especially if you're a clinician, I think it's really important because, you know, you should know the features and you should know how to communicate and counsel patients on this topic. So I also know that Dr. Lee Turner, I think, will be presenting in a few weeks or sometime after me. And so I'm going to try to concentrate more around not describing too much of the industry, but maybe a little bit about policies and practices and the, you know, patients' understandings and physicians' understandings to make it sort of more relevant to this audience. So the words unproven, unregulated, unapproved, stem cell treatment, stem cell intervention, stem cell therapy, these are all to some degree synonyms. These are terms that are used interchangeably. And there is some, I guess, difficulty with this type of nomenclature, right? What is exactly, you know, what do we mean when we say the word unproven? Scientifically unproven? Okay, well, what does unproven truly mean? Is there low levels of evidence? And in different areas of stem cell types of interventions to treat a range of different degenerative diseases, there is differing levels of evidence. Certainly in the ortho area, there's, you know, increasing evidence compared to many other specialties. You know, a lot of people use the term unproven to maybe think of it as not FDA approved, you know, synonym with unapproved, but not all regenerative products have to go through FDA approval. And I'll talk a little bit about that. But suffice to say, I think the best way to understand this industry is to just characterize and tell you what the features are. So firstly, it's an international market. These are just only a handful of countries that have been documented to have one or more of these. And I'm going to use the terms interchangeably, unproven stem cell intervention clinics. Okay. So the part that I'm going to, I'm most interested, I spend a lot of my time is to understand the misinformation, disinformation surrounding this. So a lot of the clinics provide websites, provide different types of things like flyers, social media, they advertise in many different ways. And a lot of it is actually misinformed, or in some cases, it's disinformed, meaning there's an intent to genuinely confuse or provide incorrect or inaccurate information. Some clinics have shown to, you know, try to promote disinformation by distrusting regulators, things like that. And the whole point, as I'll show in a minute, they're trying to showcase their stem cell intervention as if it was scientifically legit. And they do this in many ways. Let's look at a little bit of the marketing. So here's a flyer that I just found in Google images. You know, you have this lovely potential couple, and they're, you know, they're talking about, you know, knee injuries, the stem cells will treat arthritis, osteoarthritis, it's a regenerative medicine stem cell therapy seminar, it's a advertisement for the seminar. And, you know, little slogans like before you operate, before you medicate, regenerate. Here's the same couple. Now, actually, in another advertisement, specifically for COPD interventions in Mexico, and they're from different stem cell clinics, ProGenCell, Integra, MechStemCells, and they have different, varying different packages. A lot of the times, patients that go and talk to me that they've gotten a stem cell intervention, they've gotten all kinds of other things with it, massage, they've gotten manicures, they may have physical therapy, along with whatever condition they're treating. So, you know, a lot of times patients actually feel pretty good after one of these, you know, stem cell intervention. And here's one that I thought would be pertinent to this audience. You know, I'm not obviously a diagnostician. I don't know a lot about bone on bone. But I can tell you that this doesn't look super good. And this looks amazing after a stem cell therapy. So again, there's, you know, these types of images that are also used in various advertisements. So let's characterize this market a little bit more. So, you know, this is an older population, right? Most patients I get, you know, that have degenerative types of issues or conditions. They're, you know, older, older to elderly adults. We did a study that I'll talk a little bit about later, where we found that the average age of the population that goes and gets stem cell treatments, or at least is inquiring about it, are around 65 years. There have been quite a bit of physical, emotional and financial harms that have been documented. Pew Charitable Trust just came out, I think, last month, with a study where they looked at various different sources to find, I think, over 300 and something documented physical types of harm. And this could include, there have been death, but there's certainly been things like blindness, you know, tumors, tremors. Patients have been infected with, you know, bad stem cell or stem cell type products. And there's also been various economical and financial harms. This is obviously, you know, outside of insurance, it's a for-profit market. People pay, I've seen as low as a few thousand dollars to upwards of even 24,000 today. There used to be even more expensive. While it's an international market, it's hard to know which country has the most, but I can safely tell you that the U.S. is probably up there. And, you know, there was documentation of about 570 clinics in around, let's say, 2015, 715 clinics in around 2017. And then, you know, the market is still growing today. There's been other documents to say that's about a thousand clinics and potentially more. Many of these are physician-run clinics, and I'll talk a little bit about that from a study that we did, many of whom are not qualified. This market is evolving. You know, it used to be about certain types of stem cells, but, you know, now it's getting wider and taking things like exosomes and other types of different products as well. And patient education, so far, you know, I did a study in 2016, it's obviously older, but, you know, I don't think it's really changed. Patient education is sparse, it's didactic, and it lacks empathy. And yeah, so Benjamin, I'll actually discuss that JAMA study about the qualifications. So I've unpacked that entire paper for you guys. So I'll discuss it in a minute. So again, I mentioned that they're, you know, they're trying to showcase a lot of these stem cell interventions as if they were legit, and they do this in various ways. So clinics will, you know, advertise an award-winning board of clinical and scientific advisors. They may register their intervention as if it was a legit clinical trial on something like clinicaltrials.gov. But again, remember, this is not an experiment. They're not collecting systematic data. They're not, you know, necessarily doing any of these types of things, right? This is a for-profit business, basically, and they're, you know, selling, you know, interventions. And, you know, they may seek ethics review, they may, you know, say that they're patenting things. They'll put different types of publications to, again, showcase that, you know, maybe a mouse study that shows improvement in a particular condition. And, you know, they'll cite that, but, you know, the public may not necessarily know that what's in a mouse maybe cannot be translated into us. And certainly the way this industry is being sold is through patient and celebrity testimonials, where patients tell their story of how a stem cell treatment improved their lives. And I'll definitely unpack that right now. So in 2019, we did a study where we looked at testimonials, patient testimonials on YouTube. I don't think I really need to tell you why YouTube is such a popular social media platform. Of course, it reaches a lot of people. Being video-based, it also reaches a lower health literacy population as well. And what you may not know is out of all of the social media platforms, YouTube and Facebook are the most widely used for an older adult to an elderly population. So if a patient may, you know, go on YouTube, they will definitely find these patient testimonials. So, you know, we analyzed about 160 videos of these five major diseases, ALS, cerebral palsy, Parkinson's, multiple sclerosis, and spinal cord injury. We found that pretty much almost all of these videos were actually uploaded by the stem cell clinics. Okay. Only a handful were actually the patient talking about their own therapeutic journey and uploaded it on YouTube. But almost all of the videos were a patient talking to the viewer, which we would suspect would be another patient. So here's some metadata. You know, the videos averaged about four minutes in length, the number of subscribers. And like we've seen in other different types of studies in this space, a lot of the times the risks are rarely discussed or even undermined. Rarely are costs mentioned. And the fact that a stem cell intervention may be experimental or needing ethics or regulatory, excuse me, review. That's also a rarely discussed. So we actually coded the audio and video. And what we found was that almost 60% of these videos actually had patients acting out certain improvements. So they would say something like, oh, you know, for Parkinson's, I was able to control my tremors better. And I showed 20% improvement. And so at that time they may flash 20%. So, you know, this wasn't star Wars, there were mild special effects. And then almost in, you know, in a bunch of videos, about 67% of the videos, there was sort of this light calming music, no voices, just to sort of give this, you know, idea of, I guess, you know, a calm sort of feel. Now, I think the powerful part of the study was when we actually analyzed what the people said. So we transcribed all these videos. We, you know, then coded them using a qualitative code book and what we found. And I'll just go over a few of these 91% of the videos talked about some type of a benefit that they found. Now I'm going to show you this a little bit later, but in over a quarter of them, the patient, who's the main person talking actually said that the treatment or the provider or the clinic gave them the hope they yearn. What I'll show you a little bit later is that patients actually find that most of their allopathic physicians are kind of dismissive to their concerns and don't really understand their struggles. So, but the clinics over here and the doctors over here and in these unproven clinics did give them that hope. Another powerful motivator, which I'll unpack in a minute, over half of them praised the provider, the stem cell treatment, or just stem cells in general. And almost a third of them recommended to the viewer that they should go and get a stem cell treatment. So just to unpack praise, we you can see some of the words that are popping up here. You know, my my provider was knowledgeable. They embraced us. You know, we love them. Here's some of the quotes we found, like the second quote, I thank you and I love you because you're my extended family for making me well again from an MS patient. And, you know, some short phrases as well. So again, I think that, you know, what we concluded is that patient testimonials are very powerful and there's a pretty, you know, vast amount of literature that actually shows that narratives are much better at conveying health information than statistical information. So in this sense, you know, not only is it a great way to pass health information, it's obviously a great marketing tool by providers as well. So this is the study that Benjamin was asking about. You know, at the time, a lot of people were characterizing some of these clinics by looking at their websites, things like that. But no one looked at the backgrounds of, well, who's giving these types of stem cell therapies? There was anecdotal news reports of, you know, chiropractors and, you know, other types of complementary alternative medicine kind of folk. But no one's did a systematic search. So we decided, well, let's let's do that. So we looked at the three states that are known to have the largest amount of clinics, and that was California. It still is California, Florida and Texas. And what we did was we looked at the clinic websites. We looked at, well, who's on it? And then we basically queried state medical boards, licensed lookups. And we also looked up the Federation of State Medical Boards, the FSMB, DocInfo. These are all publicly available. So, you know, we can just look people's names up, things like that. But we also collaborated with the FSMB, the Federation of State Medical Boards, to access a, it's a closed database, but people can basically, you know, pay a small nominal fee to find out the qualifications and whatever issues their physician may have. Except, you know, we have to look up hundreds. So we decided to collaborate with them and we accessed the Physician Data Center as well. So with all these different databases, these are the results we found. So we had a total of 608 providers. You can see some of their breakdown in the different states. The first main thing we found was that a lot of these stem cell clinics were mom and pop shops. Okay. 40% were solo practices. 27% only had two to three providers. And, you know, another handful basically had four to five or upwards of six providers. And this is a pretty important finding because regulations, as I'll talk about, the FDA has done quite a bit to try to, you know, enforce this industry, but they've not been as effective as many would like. And in that sense, it could be because there's just so many of them, but they're also very small, you know, entities. And so it, you know, they may have not even heard about some of these entities. So here's your question, Benjamin. So qualifications. So we look, we found that largely the people that we found had either an MD, DO or an equivalent degree. So they were mostly physicians. Okay. And we, we saw PAs, we saw nurses, we saw these complimentary alternative medicine providers. We found podiatrists, physical therapists, and we even found one clinic. I think that was just completely with dentists. Now you got to remember these clinics are trying to showcase how legit they are. So if they're going to highlight any qualification, it'll probably be their clinicals, their MD staff. Okay. So that may, you know, these may not reflect necessarily the true numbers is what I'm trying to say. So now we focus just specifically on physicians. What we found was that this is predominantly a dude run industry, a one to 11 female to male ratio. And that most of the MD, sorry, most of the physicians were MDs as opposed to a DO or potentially a degree from outside of the country. Now we also looked at different specialties. So what we found was that among the residency specialties in the three states, orthopedics, anesthesiology, PM&R, and family medicine were sort of the top, but you can see the range of different specialties where physicians were giving, you know, we're practicing from one of these clinics. We also looked up fellowships and the top fellowships were orthopedics, pain management, or, yeah, pain management, or sports medicine as well. So the reason why this became sort of a, kind of a interesting study was because we actually tried to look at the scope of training, okay? So this was, you know, not easy to calculate because, well, we don't know who's working and what they're doing. So we couldn't really look at scope of practice, so we focused on scope of training, but we defined scope of training per clinic, not per individual, because again, if there's, let's say, five physicians in a clinic, we don't know who is doing what and, you know, who may just be there for it in an advisory capacity, et cetera. So what we did was we, so just to give you an example, let's say we have clinic number one, they are saying that they're giving a stem cell therapy for ALS and cerebral palsy. So they have, let's say, an anesthesiologist and a GP, which we can obviously find. We would say that this clinic is outside of the scope of practice because what we would have suspected, and we had clinicians, of course, coding this, was that there would be somebody in neurology or something like that that would be able to give a stem cell treatment with ALS. So we looked at the residency and or their fellowship training to see if they were, you know, qualified to give one or more of these treatments. And even if they had one urologist, but, you know, a bunch of other physicians, we would still say that this clinic would have been outside, sorry, inside the scope of training, but in this case, because they don't have one, it would be outside. And we would also consider this a non-orthopedic practice. Okay? We also found, another example would be clinic two. Clinic two gives primarily orthopedic things. So we found a lot of clinics that were, you know, doing like rheumatoid arthritis, osteoarthritis, different type of pain management for orthopedic conditions. And so let's say, you know, this case, we had a clinic that gave a stem cell treatment for osteoarthritis and knee pain, and they at least had an orthopedist or another specialist, we would say that this would be inside the scope of training and we would classify these types of clinics as primarily orthopedic practices. So if they threw an ALS in here, they would not be an ortho practice. So this is what we found. We found that overall, about half the businesses had physicians practicing within their scope of training, which meant that another half weren't. Now, the one thing I should say is that the clinics that were run completely by dentists or run completely by chiropractors, those weren't even included in our analysis. So our analysis is truly conservative. Now, when we looked at only orthopedic businesses, we found that, you know, a large percentage, 77% did have one or more physicians who practice in that clinic within their scope of training. But when we looked at the other businesses that were offering this sort of panacea of different types of interventions for all kinds of different, you know, diseases, we found that 81% of them had no physicians practicing within their scope of training. So, you know, again, this basically was sort of showing that there was a lot of people potentially giving a stem cell treatment, at least based on their residency and fellowship specialties. Certainly they could have maybe been qualified and done some research or something along those lines that we might not have been able to capture, but we found that a lot of them were practicing sort of outside of their scope of education. And so this we published in a JAMA letter in 2019. So let's, so, you know, because I'm talking to scientists and clinicians, I wanted to also give a little bit of an overview of the FDA's framework around this. So there's a nice report that came out in 2019 by the Pew. I would say that this is a great, you know, it's a, they have a short stunted summary, but they have a very nice 50 page document as well. It really covers this entire industry and what honestly every clinician or scientist who's, you know, embarking on this space should really take a read. So basically the FDA in 2017 started to clarify and produce several guidances and talk about, you know, what exactly is a human, an HCTP, which is human cells and human cells and tissues and tissue products. So they basically said that HCTPs are gonna be regulated in sort of, I'll show this in a minute, one of two ways. So HCTPs basically are intended to either basically put inside a human, implant, transplant, infuse. They could include bone, skin, adipose tissue. They could be different types of stem cells. They could be, you know, umbilical cord or amniotic fluid as well. Blood or blood derived products. So for example, PRP, platelet rich plasma would not be considered an HCTP. And then as I'll talk about in a second, cause I know, you know, bone marrow, aspartic acid, BMAC is also something that's done in, you know, the orthopedic world. If it's minimally manipulated and used for what we call homologous use, not combined with other products, it also may not be considered an HCTP. So based on risk, the FDA has basically made sort of this tiered framework, okay? And they, you know, based on regulations, there's what we call 351 regulations and 361 HCTPs as well. And 351 basically requires pre-market review and approval, meaning that if it's a 351 HCTP, a 351 product, you have to go through the clinical trials process. You have to apply for an IND or a biological license application and, you know, do a clinical trial, phase one, phase two, phase three. The FDA will then, you know, upon proving safety and efficacy, will allow marketing of that product. 361s don't require the same amount of regulation. If it's a 361 product, basically, you have to follow regulations and standards that try to prevent infection and contamination. And so that full pre-market approval process of 351 is not required. So basically, and this diagram comes from this FDA report by the Pew Charitable Trust. And so firstly, is the product an HCTP? Okay, if it's not, well, they don't, these regs don't apply. Now, is the product being taken from a patient, re-implanted in the same original form, which we have defined, and I'll have a slide of definitions in a minute, called same surgical procedure. Now, if it is the same surgical procedure, then again, it falls outside the scope. If however, and so if it isn't, well, we'll just for now forget about reproductive cells and tissues, because that's really not what physiatrists deal with. But presumably, if it's not a same surgical procedure, then these requirements have to be met. If all of these requirements are met, then it would be a 361, which means it doesn't have to do the whole FDA clinical trials process. But if it doesn't meet all of these requirements, then it does require pre-market approval. So it has to be minimally manipulated. It has to be intended for homologous use. It cannot be combined with other substances. It cannot have a systemic effect. And if it does have a systemic effect, it has to be for the patient's own use or donated to a first or second degree relative or for reproductive use. Okay, so you may have also heard terms like, again, same surgical procedure, minimally manipulated, homologous use. So let's just look at a few of those definitions. So minimally manipulated, according to the FDA, is defined for either structural or non-structural ACTPs. Structurals provide things like physical support. So for example, grinding or shaping bone would be minimal manipulation. But a lot of stem cell treatments that process adipose tissue from belly fat, things like that, they may not meet the requirements for minimal, well, they will not meet the requirements for minimal manipulation. For non-structural tissues, for example, concentrating blood by spinning it would be sort of permissible. Homologous use basically means, a lot of people thought it was getting something from this person and putting it back in that person. And that's autologous use, but not homologous. Homologous literally means that whatever you're using has to be used for that same purpose. So for example, if you were to get fat and you were using it for breast reconstruction, well, it's the same use, right? So it has to be, if you're using fat to do fat, then that's not a problem. If you're using certain types of bone product for things to do with bone, then that would be a homologous use. And the same surgical procedure exemption is basically, again, it applies for autologous use. So within that same person, it has to be in sort of a single surgical procedure and the HCTP cannot be transforming into something else. It has to sort of remain in its original form, okay? So I think this is very important for people to know, especially if they're considering practicing regenerative care. But despite the guidances coming out in 2017, despite the FDA having a sort of a period where they would be talking to patients, things like that, I'm sorry, talking to physicians, a lot of what we're still hearing is that, well, the FDA is beyond its scope. This is really the scope of practice of medicine and the FDA does not have a proper authority or jurisdiction here. But we've seen this in court cases, but in other areas as well, the FDA does have authority to regulate anything beyond minimal manipulation and things that are not used in homologous use. And that does fall within the purview of the FDA. So let's move a little bit towards what people think, okay? So I'll mention this in a minute. We have the Regenerative Medicine Consult Center at Mayo Clinic. I'll talk a little bit more about that in a minute. What we did was, at least of the Mayo at Florida, we actually got some pilot data where we asked patients just a few questions. We asked patients, 533 patients who come in just to get a consult from the Florida Regenerative Medicine sort of group there. Why are you interested in a stem cell therapy? And I'm quite sure this isn't super novel to the folks on this Zoom call, but a lot of times they wanna avoid or delay surgery. They're obviously doing this to alleviate pain or whatever issue they may have. A lot of people also think that stem cells are less invasive, which probably is the case and compared to certain surgical options, or they think it's better than surgery or maybe even better than standard of care, which the evidence does not necessarily show that, but again, it differs for different types of indications. Of course, a lot of people wanna repair, regenerate, or restore function. They wanna try an alternative, nothing else has worked. And a few people actually said that they wanna try, quote, a natural option. And interestingly, 40% of the people that contacted our consult center at Mayo actually went and contacted a stem cell clinic prior to contacting us. We also asked them a simple third question. How do you find out about stem cell treatments for your condition? So, and one of the things I'm quite sure you know is that even if it's something like PRP, which doesn't contain stem cells, for patients, they just clump everything together. For them, it's a stem cell or regenerative treatment. They may not necessarily even know the differences. So when we did ask them about a stem cell treatment for their condition, one of the things they said was that most of them, they're really, they're two sources. They do their online research. So 40% did some type of online research. And almost, again, 40% basically contacted family or friends, or they got some kind of a referral from another provider or talked to an outside provider, something along those lines. So basically they talk to people and they do their own online work. A few, but not a huge amount, almost 10% looked at social media, videos, TVs, things like that, that were non-advertisement related. A few, 5.4% actually went to one of these stem cell seminars or spoke with a stem cell clinic. And, you know, others actually looked at certain types of advertisements. So this is how a lot of the patients that you may be talking with come with some type of information prior to even possibly talking with one of you. So, you know, again, we, a lot of work has been, well, I wouldn't say a lot. Some work has been done with patients to understand their attitudes and beliefs, but very little has been done to actually talk with physicians. Other than the one study or two studies that I'm going to talk about that came from our group, there was only one other study that came from a group of neurologists. So we did a qualitative study. We interviewed 25 specialists, and you can see some of the, you know, sort of the information here in five different specialties, cardiology, ophthalmology, orthopedics, pulmonary, pulmonology, sorry, and neurology. And all of these people had some kind of experience talking with patients about stem cell intervention. So they were purposely selected that way. So we found all kinds of different things, okay? The part that I thought was kind of interesting was that when we asked people, do you think it's appropriate to give a stem cell intervention? Most of the specialists said no, okay? And most specialists, almost all specialists, only talked about stem cell treatments within their field of specialty, okay? They didn't try to, you know, think about things that happened in other areas. However, orthopedists had a slightly different view. They basically thought that in some cases, it may be appropriate to give a stem cell intervention. Most, as I mentioned, you know, thought it was clearly inappropriate, barely illegal. But orthopedists had a different view, and they thought under these sort of four conditions, it may potentially be appropriate. And so, for example, a patient has had chronic conditions, they've exhausted sort of almost all conventional options, reasonable safety data to potentially help a patient. The patients understood, you know, that they may not obviously benefit, they understood the risks, they understood the out-of-pocket costs, and of course, that the out-of-pocket costs weren't, you know, outrageous. So under those circumstances, several of the orthopedists actually thought that it would be appropriate. But even within our small cohort of orthopedists, you know, not all of them agreed with, you know, this sort of outcome. So this leads me to the sort of the last little bit of the presentation is how best to counsel patients, okay? So let's say, you know, as a scientist, sometimes I get questions from the public directly to me. Certainly as a clinician, I'm quite sure you get questions all the time about some type of orthobiologic or other type of, you know, regenerative option. So again, there's not much done. Now, this is also preliminary data that I'm about to show you. So it's just been accepted at Mayo Clinic Proceedings. So it hopefully will be published in the next, I don't know, a couple of months, a few months. So we asked the same cohort of people, we asked them, how do you practice counseling? Like, how do you counsel patients that come to you asking for a stem cell treatment? So the one thing they said is that we basically give them two approaches. We give them information. So almost all of the specialists say we give patients information. And as the sort of the first square box shows, the information could be, you know, in terms of the science of stem cells, the complexity of it. Sometimes they'll give information to set realistic expectations. And they may, you know, they'll talk about the risks, the benefits, the costs, and they may also even sometimes sit with the patient and review materials that the patient brings from, you know, their own research as well. So that's informational. Several of our specialists, but not all, and certainly orthopedists relied more on informational approaches as opposed to relational approaches. Now, relational basically means that they try to do some type of, show some type of empathy, okay? And so they acknowledge that, you know, the patient was going through a huge ordeal, it must be hard for them and their families. And so they certainly empathize, but they also, you know, reassured them that they would continue to give them care. They said, the decision is up to you, but we will support you. And, you know, again, the final decision is yours. So a lot of the physicians also use sort of both approaches. They gave them information, but they also acknowledged and heard their voices. And I think that's very important for when you do counsel patients in this space, or almost in any space. So also many specialists were generally pretty comfortable with these, but some of the junior folks, you know, fresh into, you know, becoming, some of them were in the residencies or fellowships, but some of the junior clinicians actually said that, you know, they did have some challenges and thought it would be helpful if they had some more resources. So this is interesting because, you know, this slide sort of shows, and our study shows that, you know, physicians, at least from the bunch that we studied, were very caring. Now, you know, I can tell you sort of how biases work in different types of qualitative and quantitative social science studies, but there is a little bit of a discrepancy in the messages that we get from patients. In several of the studies, including the YouTube study that, you know, we did, that I talked about earlier, a lot of patients report feeling hopelessness from their sort of the allopathic physicians. In many cases, as you can see, for example, the first quote, there was never any hope given. It was stated very clearly, actually right from the first day of the accident, that I was a paraplegic, a complete paraplegic, and that there would never be any hope at all of walking or of any movement at all below my waist. These are the types of messages that patients tell us. And, you know, I just did a couple of interviews a few days ago, just before the break. And again, the patient told me that they had just a horrible time with three of their care teams, and this patient had ALS, that, you know, it to some degree drove them. They didn't say it that way, but it appears that maybe that also pushed them towards, you know, alternative medicine, alternative types of care, including an unproven intervention. Now, certainly, physicians are busy. They don't always have the time to sit for long periods with patients to counsel them. So in that sense, I think that, you know, we should also start thinking about other people in the clinical world that may be also giving advice or counseling patients. So, you know, this could be nurses, you know, other types of clinicians, et cetera. So at Mayo, actually, in 2011, they created this regenerative medicine consultation service. And to my understanding, it is the first clinical consultation service of its kind. And as you can see, the four different types of features, it sort of does a medical evaluation. It educates patients and tries to correct any kind of misinformation. It can give clinical or research referrals when it's appropriate. And of course, it'll provide additional types of resources as well. So we, you know, we characterize this, and this came out, I think, last year, yeah, 2020. We characterized, I can't even remember how many, several thousands of these. So what happened in, basically, is this is all recorded in Epic, which is an electronic health record database. Record database. And we were able to analyze that. And what we found was that, well, this is where we found that many of the patients who seek these stem cell interventions are about 65 years in age. They live throughout the US. There's equal number of women and men. Many of the conditions there, so I think we, I can't remember, 100 and something different types of conditions that they called in for, but the top 10 conditions were, again, orthopedics. Orthopedics is perhaps out of this intervention area. I think I remember calculating the 60 or 70% of all of the unproven, if you will, interventions are around orthopedics. So, you know, osteoarthritis, certainly up there. Heart failure, COPD, cardiomyopathy, HLHS, Parkinson's, avascular necrosis, stroke, multiple sclerosis, spinal cord injury, and hip pain were some of the highest. Now, again, this, we found that I think 99.4% of the people were inquiring about a stem cell intervention. They specifically used those words. So this was a group of very high information seekers, and many of whom have already done their research, and many of whom have already contacted clinic, and some of them actually went and already got an unproven intervention. So in several cases, the consultants, in about a third of the cases, the consultants give some kind of a medical or research referral, and we also did some interviews as part of the study, and we found that many of the patients were grateful for the service and the information, yeah, about that. So this leaves me to my just last couple of slides, and then I'll just break for Q&A. So shared decision making, you know, we, you know, this is something that we hear between patients and physicians that, you know, this, you know, area where healthcare should be focused should be a shared dialogue between the patient and the physician. So what are the sort of the features that I think physicians can, you know, take home with? So certainly communicate empathically, okay? Be an active listener. Realize that, you know, it's not easy for a patient to come and talk to a clinician or even a scientist about it. I think a lot of patients may somehow know that not everything is, you know, hunky-dory with this, the stem cell field. It's not a drug that you can get, you know, off-the-shelf kind of idea. It's not, you know, completely approved. A lot of them know about the FDA. A lot of them know that these are not FDA approved. So, you know, I think it's, you know, behooves us to be active listeners and show care and ask patients questions, okay? Give them hope. Try to see if they can enroll. If there isn't a care option, try to see if there's something else that can be done. If there are any trials that could be good or other types of care options that they haven't actually tried, that they haven't exhausted. Recognize that, again, you know, patients are going to make their own decisions. It's hard for them to bring it up, and they may just make something that may be against your clinical recommendation. And then, of course, even if you're not the expert of the, you know, the unproven stem cell world, you can certainly refer patients to credible resources. The Mayo Regenerative Medicine Consult Service in Minnesota is a free telephone service. So, if you Google that, you know, Mayo Clinic Regenerative Consult Service, you will get that in the first hit. And, you know, the International Society for Stem Cell Research, they've done quite a bit, amongst other scientific societies, to create patient information tailored for patients. And they've done this in various ways. I think one of their most well-known is a closer look at stem cells, a closer look website. And so, you know, you can always direct patients to other types of sort of credible resources out there. And, of course, you know, try to avoid discrediting sources or, you know, telling patients that they're wrong, or that they don't know what they're doing. This will obviously turn them off, and they probably won't ever come back or won't be honest about anything after that. When you do provide information, you know, try to avoid technical jargon. A lot of the physicians we talked to gave sort of these principles, you know, three principles, look at the cost, look at the, you know, number two, look at the risks, look at something else, you know, simple ways of passing on information, and realize that, you know, don't be, you know, don't overstate your certainty in this. So, I hope I've been able to show that there's, you know, characterized this industry, that there's a lot of misinformation that's actually out there. And that, you know, patients will have a completely different understanding of clinical evidence, things like that. And so, they'll come with a different understanding, and potentially even desperation, when they're coming to seek something out there, an alternative. And, of course, physicians should communicate in an empathic manner, give them information, can certainly give a strong recommendation. I don't think that's inappropriate in any way, but to, you know, do that in a, you know, sort of a caring manner. And, of course, when, you know, thinking about giving care options, regenerative care options, ensure that they're evidence-based and appropriate for the physician's conditions. And then, of course, you know, ensure you're following FDA guidance. So, thank you. And some of the funding sources, that sort of funded several of these different studies, and my wonderful collaborators, who have also been most helpful. Thank you. Thank you so much. That was wonderful. You covered a lot of my questions. I'm not sure if you would like to read it off yourself, or I can definitely read them off. Okay, I can read them off. I don't think that's a problem. So, Michael Davis, is Mayo's blueprint being reproduced at other institutions, or are there plans for growing it to other regions across the country? That's a great question. So, you're talking about the consult service, Michael, I presume. So, the consult service is starting to actually, I've seen similar types of services being offered in institutions within California. And this, I think, is because the California Institute of Regenerative Medicine, which is a state-based funder for all types of stem cell research, is, you know, really trying to push things to go, you know, in a scientifically rigorous way through clinical trials into the clinic. And in that sense, they realize that patients are looking for this type of stuff. So, a lot of the sort of the UC schools, things like that, are starting to create consoles. We spoke with them about our experiences. I believe it was back in 2018, or no, probably 2019. Maybe, yeah, 2019. And so, I don't know where they are, but I think that this is going to become something that's going to become more of a norm. So, Allison, what are your thoughts about calling orthobiologics, such as BMAC or MFAT stem cell treatments, when talking to patients, even though these products have such low concentrations of actual stem cells, and we aren't even sure what drives the potential changes? Yeah. Does it just make it too confusing for the majority? I don't, so I don't have clinical experience with talking to patients about this, but I can tell you of the orthopedists that I speak with that talk and counsel patients, they do try to correct it. So, I think it's good because there's been so much hype in stem cells and everything about stem cells that, you know, I think it's good to say, well, you know, these things aren't stem cells, but they're regenerative medicine products. You know, I probably wouldn't necessarily, I don't know, I don't know if the word orthobiologic is an appropriate replacement, or, you know, just saying regenerative care or something like that. I'm not sure though, if that actually impacts patients. You know, patients, a lot of the ones I talk to, they've tried different things and nothing's really worked, or they have a very, very devastating disease, such as a terminal type disease that, you know, they're want control of their healthcare, and they're not willing to, you know, take a backseat or spend their time doing other things. So, they will try different types of experimental approaches and even unproven approaches. So, whether you call it a stem cell or not, if someone says, hey, BMAC worked for me, um, for, you know, knee OA or something else, I'm quite sure they might just listen to that. So, I'm not sure how much the nomenclature may make a difference. That's a great question though. So, Devong, do you foresee stem cell interventions becoming a potential performing enhancing medical procedure that high profile athletes use? Oh, I don't know. I do know, um, yeah, that athletes use to improve the longevity of their playing careers. I don't know if it's becoming that, or if it kind of to some degree is. Um, a lot of times I've, again, heard from orthopedists that basically tell me, you know, uh, I want what the, so a patient will come in and they'll say, I want what the athletes have. So, I think to some degree, you know, it's already been out there. Um, back in the day, we used to hear Peyton Manning, Bartolo Colon, all these, you know, famous sports players, um, getting some kind of a stem cell treatment. So, I think to some degree it's become the norm. Um, I don't know how much of a norm really it is, but I can see that, um, you know, athletes will do this. I not a sports medicine doc or anything, but from my understanding, athletes want to keep playing. And so if they can do something to, um, you know, prolong their career, I can see them trying something like that. Uh, so the next question is, okay, great. Thank you for your answer. I'm a P P G Y two at UCLA PMNR program and think it would be amazing out in California. Okay. A good comment. Uh, Victor, in your opinion has the, sorry, did I miss? No. Okay. In your opinion, has the rise in misinformation coincided with the rise in popularity of these treatments? I think the misinformation has always been there. The industry has evolved. Honestly, when bioethicists and others call on the industry and say, well, you should ensure that patients are getting registered clinical trials. Um, well, that's when people started putting stem cell interventions on clinical trials, uh, clinical trials.gov. So then, you know, we actually have to put disclaimers on clinical trials.gov saying not everything is overseen in this website. Um, I think that as bioethicists say, well, you should get ethics approval. All stem cell interventions are research and you have to get ethics approval. Well, now a lot of the clinics do that. So I think what happens is that misinformation has always been there. I think as we try to, if you will, patch up these, uh, spots of misinformation with knowledge, um, providers can necessarily sometimes, uh, find a way around that. So, um, you know, now they're, I've seen provider advertisements that actually, uh, basically say, you don't want to go to someone that gives you a hundred percent guarantee. I'll give you a realistic guarantee, you know, a prediction of how effective a stem cell intervention will be for your thing. So now they're actually kind of competing with, you know, their neighbor about, um, you know, an intervention and saying that, well, they're untrustworthy because they're just giving you, you know, way too hyperbolic claims, but I'm more realistic. So it's a messy misinformation world, but really good question. Uh, Nicole, while conducting that YouTube study, you discussed, did you come up across any YouTube channels you would recommend to patients hoping to learn more from that platform? So yes, uh, I did. Uh, unfortunately, that was the focus of my study. I can tell you that the FDA in 2020 put out a nice ad advertisement. If you just look up stem cells, FDA, it's on their website. They also have it on YouTube. I don't know if it's on their channel, uh, probably, but I'm not a hundred percent sure the international society for stem cell research, uh, Canada stem cell network, stem cells, Australia have some videos. Um, we're in the process of actually analyzing some of these warning. I call them warning messages. Um, honestly, you know, I have my own ways of thinking about the role of education and what more can be done in that front. This is predominantly where I've been focusing most of my future now, current and future research. Um, unfortunately, I find that, um, you know, um, a lot of these sort of warning messages aren't very, uh, entertaining. They don't keep your, um, you know, thoughts, uh, and focus on them. Whereas, you know, relating to a patient who has the same exact struggles as you, and they've gone through this miraculous stem cell treatment, which I call advertisements, um, generally are much better, but there are some pretty decent things out there. Um, I think that you can find out, I think most of the warning stuff isn't really on YouTube. It's primarily text-based education on websites. And unfortunately that has even less of a persuasive appeal in my opinion, then, um, you know, um, video channel. Good questions. Andrew, thank you for the knowledge. Very helpful. You mentioned several studies. Do you have a good reference for residents? Ah, yeah. No, I unfortunately don't have, I don't, I think if you can maybe get a recent review article or something like that, um, I haven't written a review, unfortunately in a really long time. There are a few out there, but not much. Andrew, you know what? I'll tell you this, that FDA report by the Pew Charitable Trust, I think is a great reference. It is chock full of actual references. It's relatively recent. It talks about the policy, but it also, you know, the first, I don't know, probably half of it just describes this industry and all of the features that I've talked about in this presentation are in there. So totally, I would recommend that one. Uh, Adam, is there any data yet regarding what specialties are primarily utilizing the Mayo Clinic consult? They're all different specialties are utilizing it. The main, uh, console, you know, the console service are, are some degree different in the Florida clinic compared to the Rochester or Minnesota clinic. Um, in Minnesota, we get consoles from all over. What basically happens is there's a general, uh, sort of a counselor, a patient navigator. If there are actual things that Mayo can do for that patient, it then gets sort of moved around or triaged to different, uh, places. So let's say there is something in ortho or PMNR or cardiac, uh, then what will happen is the patient navigator will navigate that patient towards a clinical trial, towards something else, and then sort of put it in those specialist hands to see if there's some kind of an option, maybe a care option or a research option that, uh, they can get. So it actually covers anything and everything within the Mayo system, including not only in Rochester or not only in Jacksonville, not only in Arizona covers, you know, the, the entire system. Ben, uh, from your research, do you think that the disinformation has improved now that more light has been brought to it? No, I don't think the disinformation has improved. I think it's evolved. Um, I think the narrative in news reports and stuff has slightly changed. Patients are now starting to realize that again, you know, they're, they're starting to see negative stories. It's not all about, Oh, this wonder drug stem cell treatment can cure all anymore. I think they're now starting to see that, you know, we've heard about lawsuits. A lot of the patients I talked to I've heard about the three women that were blinded in a Florida clinic, things like that. So, you know, that's, I think, um, uh, been, been, uh, brought to light, but I think the disinformation has just changed different directions. So it's just moving in different ways. What advice do you have for current residents interest in getting involved in regenerative medicine research? Um, I think that the best thing to do is to, um, you know, try to get into the research, try to understand what different types of research activities are there. And they're probably again, um, at least in, so I don't know what specialty you're in, but certainly in the orthophysiatry sports medicine world, um, there's a ton out there and it's done at all sorts of different places. So if you could do some type of a research fellowship or, uh, do some, you know, spend a certain amount of time, um, doing either clinical and, or, you know, I'm presuming you want to do clinical, but it could be basic science research. Absolutely. Just get into it. I think that will, uh, give you a greater understanding about how stem cells, stem cell biology works and how it works within, you know, us, um, because there really isn't any clear qualification on what a stem cell doc looks like. Right. So it's, it's, we're just not there yet. And covered it all in one minute after. Yes. Amazing work. Okay. Um, thank you guys again for all who've attended. Um, you guys are surpassing your peers and getting all this information and kind of understanding all aspects, which are just very important and so appreciative from Dr. Master, um, with all his knowledge tonight. So have a good night, everybody. Thank you everyone.

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