199. Dr. Jeffrey Wiegers: Stem Cells Explained—What They Can Do Now & What's Coming Next

What if medicine could do more than manage disease—and actually help the body repair itself? Regenerative medicine is moving quickly, but the world of stem cells, PRP, exosomes, and cellular therapies can be incredibly confusing. In this conversation, I sit down with Dr. Wiggers to separate what we can do today from what may be coming next. We start with the basics: what stem cells actually are, how PRP and orthobiologics work, and the difference between using your own cells versus donor-derived products. Then we go deeper into one of the most fascinating areas of regenerative medicine: MUSE cells, a unique population of stress-enduring stem cells being studied for their ability to respond to injury and support tissue repair. In this episode, you'll learn: • How stem cells, PRP, exosomes, and other regenerative therapies differ • What MUSE cells are and why researchers are so interested in them • How stem cells may respond to signals from injured tissue • Why the age and source of biological material can matter • What Yamanaka factors taught us about cellular reprogramming and rejuvenation • Where regenerative medicine is being studied for joint, cardiovascular, and other applications • The safety concerns and quality-control issues everyone should understand before considering stem cell therapy We also explore why regenerative therapies have faced regulatory hurdles, the difference between exciting laboratory research and treatments available today, and why safety, manufacturing, and proper handling are critical as this field evolves. Stem cells aren't magic—and many potential applications are still being researched. But our growing ability to understand and influence the body's own repair systems could fundamentally change how we approach injury, aging, and disease in the years ahead. Learn more about Dr. Shah: Website: drshah.com https://drshah.com Clinic: next-health.com https://www.next-health.com/ Instagram: @darshanshahmd and @extend_podcast Learn more about Dr. Jeffrey Wiegers: Website: musecellinnovations.com https://musecellinnovations.com/ Instagram: @jeffwiegers Thank You To Our Sponsor! IM8: Try IM8 today with a 30-day money back guarantee. You can get 10% off your first order with code DRSHAH at im8health.com/DRSHAH https://im8health.com/DRSHAH

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step

• 0:41Dr. Darshan Shah?

  guide to proactively avoid disease, and most importantly, extend your health span. Welcome to Extend. I'm Darshan Shah. Today, we have an incredible guest who's at the forefront of redefining how we approach chronic pain and degenerative disease. We're joined by Dr. Jeffrey Uyghurs. He's a double-board certified anesthesiologist and interventional pain management doctor, and he's a chief medical officer at Mew Cell Innovations. Dr. Uyghurs specializes in integrating cutting-edge regenerative and biological medicine with precision diagnostics to restore tissues and promote long-term health. But today, we're going to be diving deep into the world of advanced interventional

• 1:26Dr. Darshan Shah?

  regenerative therapies. I'm talking about stem cells. We're going to be talking about a new type of stem cell called the Mew cell, which is completely changing the game. We're also going to talk about cellular signaling, and how he is personally shifting his care away from doing surgeries and suppressing symptoms with medications, to actually restoring people's health. Stay tuned to learn how these innovative new approaches are changing lives, and what they could mean for the future of health. Dr. Uyghurs, this is such an incredible pleasure to have you here today. Thank you for joining.

• 2:02Speaker 01

  Thank you for having me. It's great to be here and finally meet you.

• 2:05Dr. Darshan Shah?

  I know. This has been some time coming, and I'm so glad to be here with you, because we have a lot to talk about. So today's topic is going to be around stem cells. We're going to get there eventually, though, but I just am excited to talk to you, because you and I also went to the same medical school together.

• 2:23Speaker 01

  Right.

• 2:23Dr. Darshan Shah?

  Not together, we went to the same medical school, many years apart, 25 years apart, almost.

• 2:28Speaker 01

  Right. I trailed you off in the distance a little bit. So, anyone listening, I'm relatively young, but yes, it's a great school, though. I think we both had a good experience.

• 2:38Dr. Darshan Shah?

  Yeah, it's an incredible medical school. And the reason I want to kind of bring this topic up, too, is that, you know, I have this conversation a lot with my patients. It's about, why is what we're doing here at Next Health different than what is out there in the traditional world of Western medicine? And I think one of the topics that I end up always talking about is how in medical school, I was not taught about regenerative medicine. I was not taught about even, you know, some of these functional medicine topics like gut health, microbiome, hormonal health, how to replace hormones. And I definitely don't remember learning anything about nutrition, except how, you know, certain foods affect certain drug pharmacokinetics, right?

• 3:22Speaker 01

  Absolutely. 100%, yeah.

• 3:24Dr. Darshan Shah?

  And then here I am, meeting you now, then you went to the same exact school 25 years later, which I would argue is one of the best medical schools in the country.

• 3:31Speaker 01

  Yeah.

• 3:31Dr. Darshan Shah?

  Right? Really incredible education. And what was your experience like?

• 3:35Speaker 01

  It honestly hasn't changed a lot. And I think you're at that age, when you're going through medical school, especially you being like, one of the youngest people to enter medical school, where you're just taking what's coming to you, and you're downloading it, and you're under so much stress and academic rigor, that you really don't have the bandwidth. And I don't know about you, but I was just drinking from the fire hose, that I don't think I was questioning what I potentially wasn't learning. But there was some instincts throughout the process. Looking back now, I do think there were some factors. But like you said, nutrition, exercise physiology, all the stuff that's happening on the fringe now, I was just saying, the word microbiome just really wasn't mentioned.

• 4:16Speaker 01

  And that's this whole jungle within us, more microbes than we have cells in our body, on our skin service, in our gut, all over the place. They're finding new microbiomes everywhere. There's even a conversation around, does the spine somewhat have a bit of a bacterial infiltration at times? Yeah. And then, you know, mold, Lyme disease, even parasites, were kind of mentioned as these almost mythological conditions, that one-off people, God, and maybe they did something. Parasites, it was like, if you traveled, it wasn't, it wasn't common. And I think we both kind of discovered they're far more prevalent than we learned.

• 4:51Dr. Darshan Shah?

  And you had, like, just like myself, I discovered all this through a personal journey. And like, you know, you, you kind of feel like you have an incredible amount of base knowledge to understand, but you also feel a little bit like you were almost, I would say, gypped in your medical education, because you were not taught about the real-world implication about all these things that really matter.

• 5:11Speaker 01

  Right. It was a bit of an algorithm. It is pattern recognition, which, to some degree, I don't want to totally blame the medical system, because you do have to teach, and you do have to standardize. And I think that's fair, and I still love the traditional system, having come from it. But it does need to find a way to grow. Me, personally, I think I always was a little skeptical. I was reading books like The Body Electric by Robert Becker. And, yeah, I was, I wanted to be a psychiatrist originally. I listened to, you know, or read a lot of like Carl Jung's work, and was interested in these deeper levels of health and kind of spirituality. So when I finally came up against the decision to choose, though, I was looking at psychiatry, and it was pharmaceutically heavy. And I

• 5:56Speaker 01

  think that's a fact. And I think we could grade specialties, to some degree, on how much we think they're curing, and actually building health, and how much they're covering up symptoms. And, and to me, it just wasn't, it wasn't psychiatry at that point in time. It led to a pivot. I looked at anesthesia, and, you know, all we're doing now is a little bit birthed by the biohacking movement, and all of this. And to me, I always say, anesthesiologists are the ultimate biohackers, when you think about it. Stop the heart, stop, you know, stop the lungs, control the breathing, vascular up and down. You don't have to do an RCT to watch people go to sleep and wake up. It's just, to me, it was effective. And then

• 6:37Speaker 01

  there was, and I liked that anesthesia looked at the body as a whole. They do see every type of surgery, we're touching every specialty. So there was something very holistic about anesthesia. But then seeing your surgical counterparts asked me to ask a few questions, too, of, is that person really being helped? Or is this the right, the right thing in this instance? Led me to pain management. Pain, I was a little fascinated by the devices in the minimally invasive world, which at Cedar Sinai, where I trained, we did a lot of minimally invasive for cardiac and, and pain management. And that was sort of the trend, but that's still not healing necessarily. And that's sort of that, what I was searching after the whole way. And I think probably you as well, in that, that leads into, you

• 7:22Speaker 01

  know, functional medicine, holistic medicine, and then regenerative medicine.

• 7:26Dr. Darshan Shah?

  Right.

• 7:26Speaker 01

  Altogether.

• 7:27Dr. Darshan Shah?

  You know, I look at pain management, and my experience with pain management is that if a patient is in chronic pain, that's where they are sent in order to get relief from the pain by covering up the symptoms, by using either pharmaceuticals, or, or injections to certain areas, et cetera. Most of the pain management doctors that I've known have been in that kind of world. And a lot of them, actually, you know, they end up getting into trouble for using too much prescription medication. But then there's a subset that actually try to get people better. They try to relieve the pain by getting them better, by treating the root cause of what is causing the pain in the first place, which then decreases

• 8:10Dr. Darshan Shah?

  the amount of, what have you, Vicodin, Toradol, that you have to be taking, and eventually getting off of it being the goal. And so it seems like you, you've mostly been in that latter camp, where you, you were like, trying to like, get them to get better.

• 8:23Speaker 01

  Yeah, there's, and you're, most doctors are good people.

• 8:26Dr. Darshan Shah?

  Yeah, they are.

• 8:27Speaker 01

  I do think, at the, at the end of the day. I tell people, if you want to find the most good people per capita, go to a children's hospital. Incredible people. It's just, the system almost doesn't allow them to be creative in medicine, to practice the art of medicine. And in pain management, it was that. It was kind of, I had this very restrictive menu. But then I always had an instinct that, I think me and you, if you told a, any doctor, inflammation's related to pain, stress is related to pain, they would say, yes, of course. But I didn't really have anything in the tool belt to treat from that sort of angle. And I remember, we did have one pain management physician that she prescribed or would recommend a lot of nutraceuticals. It was curcumin, and

• 9:08Speaker 01

  boswellia, and alpha-lipoic acid, that, that have evidence. And it was a little scoffed at. It was kind of, but those are, that's a drop in the bucket compared to pharmaceuticals. But you look at the data, they're comparable. To me, I do think these things, you know, there should be a reconsideration of some natural substances as well.

• 9:28Dr. Darshan Shah?

  Yeah, absolutely. Yeah. And also, you know, I think there's so much going on now with, like, a lot of the pain management occurs with like, back pain, or joint pain, knee pain, for example. I think there's a lot of incredible research also happening now, in the potential regeneration of cartilage, and avoiding surgery, and how to potentially just get people mobile faster, and mobility actually being part of the

• 9:53Speaker 01

  A hundred percent. Yeah, I think this is where now there's this, this sort of K shaped graph of some people in the regular system going the traditional way. And that's, it's just a slow decline. And then there's people that are taking their health into their own hands, realizing some of the interconnectedness, working with great providers, and you can escape that downward spiral. Not, not in every instance, but building health typically does alleviate most types of pain or most, most conditions. So I do think that old holistic saying of if you build health, you don't have to treat disease. It turns out to be true for, in a lot of instances. Yeah.

• 10:31Dr. Darshan Shah?

  So how did you come upon in your career, the field of regenerative medicine? How did you start incorporating some of these regenerative therapeutics into your practice?

• 10:41Speaker 01

  Yeah, I listened to a lot of podcasts like this first.

• 10:44Dr. Darshan Shah?

  Awesome.

• 10:45Speaker 01

  Some of the old school biohackers were on it. I was wondering, why, why is everyone going to Mexico? What's happening down there? And then luckily, when I was in fellowship, there's a pretty good orthobiologic scene in LA. So I bumped into the Toby conference and some of the regenics people and started to learn about the autologous. And for the listener, autologous is just a word of coming from yourself, using your own materials and repurposing them. So things like platelet-rich plasma and bone marrow and, and fat, nano fat, people were using as regenerative products. And at my fellowship, a lot of people were going to the device conferences and I was going to the orthobiologics conferences. And that was revealing. I think that was a step in the right direction. If you find people

• 11:29Speaker 01

  using orthobiologics, I think they all feel pretty good in their heart about what they're doing. But then it was still a journey of, of, there's this awkward period where I think there's some very exciting things happening in the lab that we see these headlines. Stanford did this, or whatever it is. And that's, that's off in the future. And then there's what we can do today. And there was a bit of a gap. And to me, it became this journey of kind of troubleshooting what is available, what's out there, what's being underestimated to try to problem solve until all these, you know, miracles that we hear about are going to make their way to the clinic.

• 12:04Dr. Darshan Shah?

  Yeah, yeah. I'd love to talk a little bit more about orthobiologics. Like define, like what are orthobiologics and what are they used for?

• 12:13Speaker 01

  Orthobiologics essentially, or biologics in general, just being materials naturally sourced. Orthobiologics, we're usually talking about things from the mesenchymal lineage. So the, in development, there's three germ layers, ectoderm, endoderm, and mesoderm. Mesoderm being the, the middle layer, which develops into bone, muscle, cartilage, all the connective tissue. And most times when people are using targeted injections, those are the tissues we're trying to rebuild. And so orthobiologics is essentially taking tissues that are familiar to that lineage and repurposing them from, say, whether it's distilling the blood for plasma, or taking, say, bone marrow and trying to, to get the

• 12:57Speaker 01

  stem cells out of there and then use them for, for healing.

• 13:00Dr. Darshan Shah?

  Right, right. So PRP, I think a lot of people have heard about it for joint injections, specifically, and also cosmetic reasons as well. How does PRP work? Like, what is in the PRP, platelet-rich plasma that we're injecting into our joints that relieves pain? And, you know, I could tell you from my own personal experience with my parents, both of them have been using PRP for years when they were told they need a joint replacement and they're just, they've avoided joint replacements from it.

• 13:25Speaker 01

  Yes, that, that's amazing. Good to hear. PRP, there's actually a little bit of a question mark still on what exactly, we know the platelets are playing a role because you see higher concentrations of platelets tend to be more beneficial. Who and what are platelets? When you have an injury, they're the first guys on the site. So we say that they pull the fire alarm on an injury. And by doing that, they release these granules that are essentially a package of setting off the cascade of healing. They're recruiting other factors within the immune system to that site. There's a little bit of a question of, are the white blood cells that we're capturing in a PRP mixture playing some role as well? That's where people talk about leukocyte-rich or leukocyte-poor PRP. And, and we do know

• 14:08Speaker 01

  that things like macrophages are integral to, to healing. But essentially, back to the analogy of the fire alarm, you pull the fire alarm, the immune system and the whole construction team shows up on site, they kick in a construction site. That, you'll often hear people get some PRP, there's a little bit of a flare up afterwards. And then the healing's kind of progressing from there. And then they say they potentially feel better. The rate limiter on PRP is we do know as you're aging, the potency of your own plasma and your platelets is going to drop to some degree. Your healing capacity drops with age. And so after, they say about 40 years old, there's a bit of a parachute effect where PRPs may be becoming

• 14:50Speaker 01

  less effective. So that's, we're dependent on the source material.

• 14:54Dr. Darshan Shah?

  Right, right. Absolutely. And, you know, to that point, there's other therapies that are similar. Like I've heard of regenecine, for example. Is that one of them as well?

• 15:06Speaker 01

  Yeah, regenecine is kind of in the, it's, it's one of the first, you know, there's different ways that they distill essentially the, the plasma and the platelets and isolate different factors. And, you know, people are out there fighting in the streets saying, this one, you need a lot of this factor, you need none of that factor. And everything that's a small community becomes a little culty. And so it's kind of a bit of that.

• 15:28Dr. Darshan Shah?

  I see. So, so what are some of the other kind of options around just injecting plasma? So there's PRP, there's regenecine, are there others as well?

• 15:37Speaker 01

  Platelet lysate is essentially a more, it's cleaned out a bit. It's just mostly factors in plasma. It's, it's less cellular material, which some people say for certain sensitive areas, it's nicer to have like a lysate that's a little bit more just pure growth factors.

• 15:53Dr. Darshan Shah?

  Got it. Okay. And so when someone's experiencing pain, usually joint pain, they can go to like a pain management doctor and ask them, what do you think out of all of these therapies would be the best one?

• 16:05Speaker 01

  That's right. Yeah. So then that's a conversation I end up having every day. And there's two, this is where we hit this division between autologous sources, coming from yourself. And I would say that the most common are PRP, which is very easy to obtain. You're just drawing blood, bone marrow and, and fat. And those are kind of the three key sources of mesenchymal products, or PRP being a little bit different. But then there's allogenic. So this is a source that is not your own tissue, but it's being either processed in some way, or it's an off the shelf product that you're then implementing for healing. And that gets into a whole, kind of another bag of, of issues in processing and manufacturing.

• 16:46Dr. Darshan Shah?

  Right, exactly. So autographs, meaning coming from yourself, you're doing like a tiny liposuction procedure, getting some fat out, you're maybe putting a needle in their bone to get some bone marrow out, or you're drawing their blood to get the plasma out. So you, it's coming from your own body. But to your point, the efficacy of that probably isn't as good as something coming from like maybe a baby, because you have multiple years of aging that has accumulated in those products. So there's not going to be as efficacious. So then the other thought is then to use something that comes from a much younger individual, is that right?

• 17:19Speaker 01

  Yes, yeah. Generally, if you're going to use some sort of allogenic product, this is coming from young sources and, and sources, meaning the most common, I'll just go ahead and lay this out, is people using like umbilical cord products, which I don't want people, there was kind of this whole, you know, in the Bush era, what's going on? Ethics kind of question, these are factors that would otherwise be disposed.

• 17:41Dr. Darshan Shah?

  Yeah, they would have been thrown away. The umbilical cord and placenta is always thrown away. So instead they get donated, or they get sent to a lab in order to get the same platelets or granules or other products, mesenchymal products, that we can use that are donated from another individual, right? Come from another individual. But people will always ask them, like, well, if they're coming from someone else, isn't that dangerous? Isn't there a risk of infection? Isn't there a risk of, you know, this not being compatible with my body? So how do we talk about that?

• 18:11Speaker 01

  Yeah, this is not, we're, we're doing the, I like the, this is a history lesson. We're doing, we're adding the history lesson here. So when I entered the scene in the regenerative space, that was the biggest question to me. Okay, but those are going to get rejected. We've seen transplants before. We know that organ tissue is rejected. That is actually true for most of these products. And so what a lot of people started to do is you can take a stem cell, which is a living cell, and we'll get into what exactly a stem cell is. And some people would use the cell itself, but cells are always producing factors. They're always producing a natural function of a stem cell in the body. It's producing other cells. And then it's also kind of being like a cheerleader for the region. It's, it's keeping everyone else healthy and kind of mothering the region in general. And so you

• 18:57Speaker 01

  can take all of those factors it's producing, and I call that kind of, that's kind of a bone broth. The, the technical word is the secretome. And so some people started to say, okay, the cells are rejected, let's not use those, but we'll take this secretome, all that bone broth, and we'll either select certain factors out of there. And there's once again, a million ways people are doing this. Or you can take that whole secretome and, and people may have heard the word exosomes. Exosomes are a component, they're a nanoparticle within that secretome that people then would utilize a lot of the time. And that was not rejected. So for a while, that was one of the troubleshoots, was let's move to exosomes. And I'll go ahead and say, we will talk about the desawa mu cells as a particular factor.

• 19:38Speaker 01

  And I think let's, we can lay out some more of this groundwork, but that is one key fact that's going to get very interesting here, is that they do troubleshoot this whole issue of rejection.

• 19:49Dr. Darshan Shah?

  Right, right. Yeah. So, you know, there's this whole I would say cottage industry of people taking those umbilical cords and extracting from them the stem cells, whether the mesenchymal stem cells from some of the umbilical cord tissue, or they're extracting even the blood and the hematopoietic stem cells from there, and then making those into products. What about those products?

• 20:14Speaker 01

  Yeah, they're a level more potent, in my opinion. In these younger lineage products, they're producing a wider array of growth factors and healing factors, whereas what's floating around in your plasma is somewhat limited. And people have done analysis of everything that's included within there. And when you look at a pure secretome or exosome product, it's very potent in a large array of regenerative factors. And you're also getting a level of consistency. If you're grabbing just your plasma, just 80-year-old plasma is going to be, it's just not that potent. Whereas, we know that those younger materials, we can look at it in a lab, we can standardize. So that, to me, is something

• 20:57Speaker 01

  that is going to be more consistently beneficial.

• 21:00Dr. Darshan Shah?

  In the future, right? And I think, and this is where, like, a little bit more of the politics around the stem cell industry comes into place, because it seems like to me, instead of using your own allograft stem cells that are older and probably not as potent, you have these potent ones that are in massive supply abundant, because there's like an unlimited number of umbilical cords out there, right?

• 21:22Speaker 01

  Right.

• 21:22Dr. Darshan Shah?

  But for whatever reason, the FDA seems to have frowned upon this being used as a potential therapeutic intervention, more so than even your allograft stem cells. So I'm just wondering, like, why? And where does that come from? And what is the politics behind some of that?

• 21:41Speaker 01

  Biologics have particularly struggled to get through the FDA pathway for a couple reasons, in my opinion. The biggest one is standardization of a product. So I say all the time that making a drug is kind of like baking cookies, where it's essentially the same thing every single time, same molecule, same single molecule, you just print it. Whereas, stem cells are a little bit more like vintages of wine, the weather and the conditions, and everything is going to cause some difference. And, you know, you're talking about donated genetic material, and it's going to vary slightly from batch to batch. So the FDA will ask the question a lot of the time, how do you know, though, that this

• 22:22Speaker 01

  batch is the same as that batch, is the same as the next batch, which is a valid question? But it is ultimately a barrier that, to me, as long as a cert-- that's why an exosome product, okay, that's why people are trying to characterize, and that's the circumvented way we're having to try to get these things approved. And obviously, that takes a long time and a lot of money.

• 22:43Dr. Darshan Shah?

  Yeah, yeah. Also, you know, like, I'm tracking right now, it's happening live today, actually, as we speak, the FDA hearings on peptides, right?

• 22:51Speaker 01

  Right.

• 22:52Dr. Darshan Shah?

  And to me, also, it goes beyond that in some of the massive over-influence that the pharmaceutical industry has on the FDA as well. Like, if you're watching these, the people that are vehemently opposed to peptides being approved are these not-for-profits that are all totally funded by the big pharmaceutical agencies, right?

• 23:13Speaker 01

  Absolutely. Yeah, yeah.

• 23:15Dr. Darshan Shah?

  And so it doesn't, it doesn't help the pharma industry to have something like a stem cell or exosome product out there that could potentially negate the need for pharmaceuticals completely.

• 23:25Speaker 01

  Totally. Yeah. You know what else it does that they don't love, is causes people to heal. A lot of, in a lot of ways, which is a big factor here, because in clinical trials, actual regeneration's not that easy to measure. It takes longer.

• 23:40Dr. Darshan Shah?

  Yeah.

• 23:40Speaker 01

  It takes six months to a year, and maybe repeated courses a lot of the time. Whereas, what's really quick and easy to measure is what pharmaceuticals are good at, just knocking down a number in the short term. Like, a corticosteroid is quicker at getting rid of inflammation, but in pain management, we've learned inflammation's part of the healing process. And even, like we were talking about PRP, a little bit of a flare up, a little inflammation, leads to gain in the long term.

• 24:09Dr. Darshan Shah?

  Yeah.

• 24:09Speaker 01

  How do you measure it? It's tougher. And so it's been a barrier in clinical trials, too, because endpoints are almost set for a drug model.

• 24:18Dr. Darshan Shah?

  Absolutely, yeah. And the other problem, too, is I think there's this whole idea of manipulation, right? So the minute you take one of these biological products, even if it's an allograft, and you do anything to it, now all of a sudden, it's deemed a drug, because it is no longer a biologic material, it's now a drug, because you manipulated it in some way. And therefore, you need to have one of these, like, incredibly expensive trials to treat it as a drug and put it through the system as a drug.

• 24:45Speaker 01

  Yeah, absolutely. I mean, it's gamification is kind of the thing. It all is very gamified. It's pay-to-play, to some extent. And there's a lot of doctors that want to do trials. They just, you really have to go around with your, you know, bull begging for millions and millions of dollars to get the trials done. And pharmaceutical companies have a pretty good idea if they're going to push something through to the end. They are very good at betting on horses at this point in time. And they don't like when you bet on a horse and it fails. And that's where I think a lot of people with peptides, for example, are willing to say, I want to bet on this, though. Like, I've seen a difference. And it's just, you see how many people want it, but it's still hard to get the money together. I think clinical trials will change. I think a lot of this landscape will change.

• 25:30Speaker 01

  And I think safety's going to become a bigger word. I think we have to weigh safety, bias towards safety, and then if safety's intact, we can start to do more real-time clinical trials with a bit of a commercial environment.

• 25:43Dr. Darshan Shah?

  Hundred percent, yeah. I totally agree with that. You know, the other thing I think about with the whole stem cell industry, and I want to get your opinion on this, too, is like, some states are not waiting for the government, the United States federal government to catch up. And they've said, like, look, we're going to do our own laws around stem cells, Florida being a perfect example right now. What have they seen and done differently that allows broader use of stem cells in Florida?

• 26:08Speaker 01

  What have they done, like, legislation-wise to allow it? So they've essentially said, as long as the manufacturing is up to par, which meaning these products have to come from certain labs that are vetted and using, have a certain degree of oversight, then they will allow those products to be used. I think really what they're doing is allowing us a chance to be on good behavior. And hopefully, and there's, you know, we can't lie, there has been some bad cases in the past where people have gotten injuries mostly due to medical negligence and not applying products appropriately. I truly do not know of a case where everything was done correctly and there was an injury. So they're giving us a chance, and I'm just hoping no one overfishes the pond and gets greedy. We all have to kind

• 26:51Speaker 01

  of be in this together, is I think what us in this community feel.

• 26:55Dr. Darshan Shah?

  Exactly. So a lot of the advancements in stem cells emanate out of Japan, actually, now. And I feel like Japan, since Yamanaka won the Nobel Prize for his discovery, all the Yamanaka factors, which we should talk about, too. I'd love to hear your take on that. They've really leaned into creating a regulatory environment around biologic materials and stem cells that is different and leads to more innovation and more discovery than we have here in the United States, right?

• 27:26Speaker 01

  Yeah, correct.

• 27:26Dr. Darshan Shah?

  Can you talk about that a little bit? Like, what have they done differently?

• 27:29Speaker 01

  They're kind of doing what Florida, to some extent, has done. Essentially, they're accelerating clinical trial pathways by weighing heavily on safety. They've said, if you can demonstrate safety, then they can move quicker through the rest of those clinical trial pathways, which I think is a pretty reasonable thing to do. I mean, you'd anticipate a few things that get farther, maybe, than they should have, but maybe some stuff that wouldn't have gotten a chance is going to make its way through, which I think there's a need for.

• 27:55Dr. Darshan Shah?

  Yeah, I totally agree. And so, let's talk about Yamanaka real quick, because we're going to do a little bit of history on a few Japanese people today as well in this podcast. But tell us about what Yamanaka discovered and why it's so important.

• 28:08Speaker 01

  Right. So I'll lay out, I'll do the stem cell part of stem cell 101. What is a stem cell? A stem cell is an undifferentiated cell. It hasn't picked a job in life. It still has the ability to go down different pathways of differentiation or becoming different cell lines. The other thing they do is they self-renew, which, there's two types of self-renewal, symmetric and asymmetric. Symmetric means it just clones itself. One stem cell becomes two. And then asymmetric is a stem cell creates another stem cell, and then a progenitor cell, which is going to go down a cell line. So like in your stomach, for example, the stem cells there are creating another one of themself, and then sending one down the

• 28:49Speaker 01

  line to become like a stomach cell, essentially. So all stem cells have those two characteristics, and that's the definition of a stem cell. And so a pluripotent stem cell can become any cell in the adult human body. A multipotent stem cell can only become kind of a more confined range of cells, like we were talking about with the orthobiologic and mesenchymal stem cells. What Shinya Yamanaka discovered, there was four factors that he said, I think if I give these factors to a cell, I can turn a differentiated cell, a cell that's already picked its job, back into a kindergartner, essentially, into something with no job

• 29:30Speaker 01

  that can choose again. And so he unlocked, it was a fibroblast they first did it on, and they gave it the four factors, and it morphed it right back into a stem cell that then did not have a job again.

• 29:41Dr. Darshan Shah?

  Yeah. And it's just crazy, because we, for-- Decades, maybe, you know, even fifty, sixty years, believe that there's no way that would happen, right? That's not possible, right?

• 29:52Speaker 01

  Right. It was deemed as very risky. Like, this is, this is some of the stuff of why, why would that ever exist?

• 29:57Dr. Darshan Shah?

  Right.

• 29:58Speaker 01

  Within the, and this is when, um, you know, there's kind of a movement to me happening of DNA was like the king of, of everything. That's where all the intelligence was held in the cell. And now we're kind of discovering like the cell is very intelligent itself. It, it turns on and off its genetics and it can adapt to situations. So the cell's the intelligent machine, not just the DNA.

• 30:19Dr. Darshan Shah?

  Right.

• 30:19Speaker 01

  We can also signal and, and give it instructions if we convince it to.

• 30:24Dr. Darshan Shah?

  Yeah, yeah. And then those four Yamanaka factors, are those proteins? Are they peptides? What, what are they?

• 30:30Speaker 01

  I believe it's proteins. I know it's, it's oxox, uh, cemic and kaileph.

• 30:36Dr. Darshan Shah?

  Right. Those are the four Yamanaka factors. And I know there's a lot of research going on right now about harnessing those factors and having cells go backward, but not all the way to pluripotential. For example, David Sinclair at Harvard is doing the study on that, on the first human clinical study is launching on eye cells, right? On, um,

• 30:54Speaker 01

  Yeah.

• 30:55Dr. Darshan Shah?

  optic cells, optic neuron cells.

• 30:57Speaker 01

  Yeah, this is, um, what they're calling this is cellular rejuvenation. Essentially, they took cemic out, which was the most carcinogenic, or it's a known oncogene, it can cause cancer. So they said, uh, what if we take cemic out and we just give the other three? What will happen to cells? And they've seen that even those three alone caused not a pluripotency, but a rejuvenation, essentially a, a backpedaling of the clock.

• 31:20Dr. Darshan Shah?

  Yeah, yeah. Pretty, pretty, pretty interesting. And then also, um, you know, there's a company called Retro Biosciences. Have you been tracking them?

• 31:27Speaker 01

  I don't think I know this one.

• 31:28Dr. Darshan Shah?

  Oh, yeah. Retro Biosciences is a OpenAI, Sam Altman funded company, um, out of San Francisco that are modifying the Yamanaka factors, um, using AI and creating thousands of different versions to really accelerate the process. Because I think one of the problems with the original Yamanaka factor proteins is that only, um, they only work a very small percentage of the time. So it takes a lot of trial and error. And with the new versions, kind of like with, you know, the, the change that they made to the GLP molecule, just being able to last longer, therefore it's effective now. We have these major drug categories of the GLP ones. Um, they've done the same with the Yamanaka factors and created more consistent and better

• 32:11Dr. Darshan Shah?

  working versions. And so now they're going to clinical trials as well in Australia.

• 32:15Speaker 01

  That's amazing. I love that. And this is earlier on, I was talking about the things you hear, the headlines that are, that are coming for us. Um, yeah, that's actually very, very exciting. I'll have to look them up.

• 32:25Dr. Darshan Shah?

  Yeah, this is all extremely exciting stuff because I think there's a world that's going to happen during our lifetime.

• 32:32Speaker 01

  Right.

• 32:32Dr. Darshan Shah?

  Where we're harnessing the power of these stem cells and peptides. And so

• 32:35Speaker 01

  Yeah.

• 32:36Dr. Darshan Shah?

  I think that, um, you know, the, the pharmaceutical industry, everyone knows is massive, but the stem cell industry and peptide industry, in my opinion, will be just as massive in the next ten to fifteen years.

• 32:45Speaker 01

  I completely agree. You have to treat the materials as smart, though. Like, to some degree, it's, it's a conversation with the cell.

• 32:52Dr. Darshan Shah?

  That's true.

• 32:52Speaker 01

  Where, um, I'm obsessed with this guy, Michael Levin's lab, where he's bioengineering tissues and, and, and one thing he says is you have to convince the material to build something. And then it will, if you can convince it through, he uses a lot of bioelectrics. And I, I look at cells themselves in that manner. If you mess with them too much, they can start doing crazy things. And I think that's where this iPSC induced pluripotent stem cell research has been slow moving is if you tinker too much, it can go into identity crisis.

• 33:21Dr. Darshan Shah?

  Sure.

• 33:22Speaker 01

  Almost. Yeah. And, and I do think the cell is always, like our body's always trying to heal itself. It's so, the cell always adapts to the environment it's in, right? It's a, and, and I think if you have a cell in a dish and you're manipulating it too much for too long, it's kind of like, who am I and where do I belong again? And, and I think that's where, you know, a lot of these, then you put it in an organism, it might say, I don't know any of you guys, and I'm going to fight for myself. And that's kind of the, the cancer moment.

• 33:50Dr. Darshan Shah?

  And that turns into cancer, right? Exactly. And so to your point, like, this is one of the dangers about, uh, stem cell therapy and not having the research out there is when does the cell provide benefit? And when does it turn into something that'd be potentially a huge problem, like a cancer?

• 34:05Speaker 01

  Yes.

• 34:05Dr. Darshan Shah?

  We need to, we need to be really clear on what are the manipulations we can and can't do and in what environment?

• 34:10Speaker 01

  Yeah. This is like the, my favorite thing about humans is we find something and we think it's going to be simple and we make this mistake all the time. And then it ends up taking a long time because we underestimated the, the thing in the first place. And I think iPSCs is one of those.

• 34:23Dr. Darshan Shah?

  Yeah.

• 34:23Speaker 01

  I actually still do some research at Cedars-Sinai, where we, we take, uh, iPSCs that are nucleus pulposus cells, and we try to regrow the spine. And it's, you know, it's, it's a difficult game. You're, you're trying to regrow and they're, they're mastering the programming of the cells. But then now will it take to the environment when you drop it in? And, um, it's just troubleshooting all the way down.

• 34:43Dr. Darshan Shah?

  Yeah, exactly. Didn't Cedars, um, just get a massive donation to start a regenerative medicine, uh, research facility?

• 34:51Speaker 01

  Yeah, they have the Regenerative Medicine Institute.

• 34:53Dr. Darshan Shah?

  Yeah.

• 34:53Speaker 01

  Which I think is, uh, California has a big regenerative medicine fund. And I think they're the top recipient of, of grants from that fund. So there's a lot going on there. That was one of the early things that kind of put me onto the, the scene here.

• 35:06Dr. Darshan Shah?

  Yeah. Very cool. Very cool. So let's talk about another Japanese scientist.

• 35:10Speaker 01

  Yes.

• 35:10Dr. Darshan Shah?

  Dazawa. Who is Dazawa? And what did, what did she find?

• 35:13Speaker 01

  So actually around the same time as the iPSC research with, uh, Professor Yamanaka was Mari Dazawa. And, uh, she really by accident, as these things happen in, in science to some extent, was growing cells and accidentally mixed reagent she didn't mean to came in the next day and found that only this one specific cell population had lived overnight. And she didn't just, you know, throw them away. She started to look into these cells and she was a little bit questioning why those cells in particular survived. Um, and turns out that they were a unique cell line that actually exists within all of us. And we'll get into the characteristics on them. But from there, she continued to research and,

• 35:57Speaker 01

  and she pushed through, uh, human clinical trials. And there's actually a pretty large body of data that I think there's, there was a bit of skepticism historically around because it had been a foregone conclusion that there was no pluripotent cell, there was no cell with these sort of characteristics in the adult body. But some people had kind of claimed eureka in the past. And then Mari, um, fortunately pushed down through the research pathway enough that, uh, now they're actually very well characterized and, and fairly well understood.

• 36:27Dr. Darshan Shah?

  Right. And so these cells that, um, that Dazawa, uh, described, they're called MUSE cells, M U S E, which is an acronym for what?

• 36:36Speaker 01

  Multi-lineage differentiating stress enduring.

• 36:39Dr. Darshan Shah?

  Right. Okay. And so what does that mean?

• 36:42Speaker 01

  Yeah. Essentially, she named, you, you named these things early, right? And she named them because they survived in extreme stress.

• 36:48Dr. Darshan Shah?

  Got it.

• 36:48Speaker 01

  So she said, these guys are stress and are enduring. The differentiating, which is not in the acronym, but differentiating because she also noticed that they were pluripotent. And like we were saying earlier, they can become all three cell lines or major cell lines in the human body. So they can become heart and liver, they could become stomach, they could become a nerve, they can become a bone.

• 37:09Dr. Darshan Shah?

  Got it.

• 37:09Speaker 01

  They have all options open and that was a very unique characteristic.

• 37:13Dr. Darshan Shah?

  Yeah. And so, you know, I think when you hear about stem cells and you talk about this pluripotential stem cells that we all have, you assume there's just like one type of those. But it sounds like there could be sub families of

• 37:25Speaker 01

  Yes.

• 37:25Dr. Darshan Shah?

  stem cells as well. This MUSE being one of them. Why is that?

• 37:29Speaker 01

  The why is, that, that's the good part right there. Man, if I had the answer to that one, we'd, we'd be on to something. Yeah. The question is why? But I think that's the big moment with MUSE is that we are learning there are these sub lineages.

• 37:42Dr. Darshan Shah?

  Yeah.

• 37:42Speaker 01

  They are very similar to certain cells in the immune system. I actually think of MUSE cells almost as a hybrid between a macrophage and, and a true stem cell.

• 37:53Dr. Darshan Shah?

  Okay.

• 37:53Speaker 01

  One thing that's important to explain here is all cells in our body exist within a niche. So your knee is a niche. That's like a neighborhood. Or that's like, let's call that Kansas City, right? Like, that's the, the Kansas City niche is the knee. And then you've got the heart and you've got the brain. And only certain, I, I actually think there's a really great analogy that your whole body's kind of like a country. And, and it's a, it's an ecosystem and it likes to know all the citizens and where they're at. And so if, that's why if you take fat and you transpose it into the knee, it might give some regenerative signaling. But even if, even if it's your own, it's not supposed to be there. So it will get eliminated by your immune system. Now, there's a few systems

• 38:34Speaker 01

  in the body that touch all areas, all different niches, one of them being the immune system. Your immune cells do make their way into any neighborhood anywhere because they have to. So they sort of have a universal passport. MU cells have that as well. And they really are, it seems like, the emergency response team

• 38:54Dr. Darshan Shah?

  Got it.

• 38:55Speaker 01

  in an injury. So there's certain injuries that are small. And say, the local police, the, the stem cells within that niche can heal that. That would be, you work out, you tear the bicep muscle a little bit, but it's going to grow. But all just the local guys can handle it. Then there's a broken bone. That's a more catastrophic injury. You're going to deploy more immune cells. And that is an instance in which it might meet a certain threshold to which MU cells are now going to deploy and make their way to an injury like that.

• 39:24Dr. Darshan Shah?

  Got it, got it. So yeah, so these are highly specialized pluripotential stem cells that kind of function like immune cells in that they can go anywhere in the body to help heal. And that's one of the reasons they're so interesting. Another reason they might be interesting is when you look at them under a microscope, they look different than other pluripotential stem cells, right?

• 39:45Speaker 01

  Right, they do. They, all stem cells are particularly compact. They stay in a state of quiescence, which is essentially they're in a homeostasis of, they're kind of grooming themselves. They're, they're making sure they're as healthy as possible. They're making sure they don't have genetic defects. They're, they're, you know, taking care of their telomeres. Because their job is really to wait until they're needed. Um, and that's how you see MU cells. They're a very small, compact stem cell, just waiting for an emergency, essentially. Um, they're found all over the body, but mostly within the bone marrow. And they're sort of hanging out in that area until, uh, they're needed to deploy.

• 40:21Dr. Darshan Shah?

  Got it, got it. And do they have, you know, you talked earlier about these little packets that they all have inside of them called exosomes, or in a secretome that they secrete, that has a lot of the effect of them, that creates that healing milieu in the areas. Do they have more of those or different types of those inside of them?

• 40:39Speaker 01

  Yeah, it's a great question. We have actually characterized the secretome of MU cells. There are some unique factors compared to just a regular mesenchymal stem cell. Uh, I believe it was eighty something different factors. The, the summary on them would be they're higher in certain resiliency and survival factors, uh, which, coming with the stress enduring, they, they seem to be the most resilient cell. And it matches that they actually secrete a lot of resiliency factors. So if they're like, kind of the crisis management team, it would make sense that they're saying, you know, hang in there, guys, uh, is sort of the, if we put words to what they're messaging.

• 41:16Dr. Darshan Shah?

  Got it, got it.

• 41:21Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen thirty year old people with cells that look like they're pushing retirement. And I've also seen sixty year olds with cells that look like they're forty years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells you see are like phones and they have limited cell phone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IM8. IM8 powers that cellular battery. It's not just another multivitamin. It's a comprehensive ninety-two ingredient formula, designed specifically for cellular health and longevity.

• 42:06Dr. Darshan Shah?

  I'm talking nine hundred milligrams of vitamin C. That's like twenty oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IM8 actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IM8 had partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies. And they've gotten this NSF certified to truly power your health.

• 42:48Dr. Darshan Shah?

  Most people are aging twice as fast as they should, unfortunately. You don't have to be one of them. Try IM8. I actually have a discount secured for you if you go to drshah.com/ima or go to im8health.com/discount/drschaw and you can get twenty percent off with my discount code, Dr. Shaw. You can also find the link below.

• 43:12Dr. Darshan Shah?

  So you know, one of the things, um, that people always talk about with stem cell therapy, specifically like these MU cells, for example, they, they would come from the umbilical cords as well, right? You wouldn't be able to take these from your own fat or bone marrow?

• 43:25Speaker 01

  You can.

• 43:25Dr. Darshan Shah?

  You can.

• 43:26Speaker 01

  You actually could, yeah. And this is a discussion we have internally to, to some extent right now is what's the best sourcing? Uh, Dr. Dazawa's studies, she was mostly studying bone marrow MU cells.

• 43:37Dr. Darshan Shah?

  Got it.

• 43:38Speaker 01

  Now, back to before when we were saying, are younger products more potent than, than aged products? That's where there is a discussion and we do think, well, if you're going to have a MU cell, you probably want the youngest MU cell. So they're probably more potent when taken from something like a, you know, an umbilical tissue.

• 43:56Dr. Darshan Shah?

  Got it, got it. But so to your point though, you can still extract them from the bone marrow of an adult as well, right? And it's really just that Dazawa is more of a process to get the actual, this, this one stem cell population from all of the other cells.

• 44:11Speaker 01

  Yes, yeah. To, to give people transparency on sort of how this is playing out. There's a company called MU Cell Innovations that, that I'm the chief medical officer of. And MU Cell Innovations is the continuation of Mari Dazawa's research, uh, essentially. They own the global patents and, uh, an important thing to know is they've also, all those factors that are secreted from a cell, our CEO, Dominic Duscher, has studied this before. And, and when you take a cell and the moment you put it in a dish, it's going to behave a little bit differently than it would have in the body. And then the more things you do to it, the more it's also going to change what it's doing. So the Dazawa process is really, how do you isolate MU cells?

• 44:53Speaker 01

  Grow MU cells, but not change their character along that process? Cause you could do a lot of things to a cell. You could start with a MU cell even, but you could do things in a dish that cause, you know, a crazy different cell lineage that is, is either potentially dangerous or at least maybe ineffective. So we want to preserve all these special qualities of the MU cells. And that's why we do designate Dazawa MU cell.

• 45:18Dr. Darshan Shah?

  Got it. Yes, it's so interesting what actually transpires in a lab around stem cells. Because to your point, these are organisms, they, they can be encouraged to do some things or not. And we don't know until we actually like, look at them and, and use different factors to see what happens, right?

• 45:35Speaker 01

  That's right.

• 45:36Dr. Darshan Shah?

  Yeah.

• 45:36Speaker 01

  And that's how we know this process, how we know that we're ultimately doing that process. Yes, we look at all the factors they're secreting and what they're messaging. But the product, the Dazawa MU cell product is the product that all the science was based on, all the animal studies, all the human trials that are coming out of Japan. It's all based on this process exactly, so.

• 45:54Dr. Darshan Shah?

  You mentioned they were smaller, like how much smaller are they than a pluripotential stem cell?

• 45:58Speaker 01

  Quite small. The measurement I don't have off the top of my head, but, but they're small. And one of the factors that comes up is a traditional MSC, a regular, uh, mesenchymal stem cell, is known to get trapped in the vasculature of the lungs. And, and people want to look at this as just a conversation around size. But one thing I'll say, like a, a macrophage, an immune cell, is actually too large to pass through that capillary. The way they pass through a capillary is they thin themselves. They, they manage their cytoskeleton to become more oblong and slip through. Um, something like a mesenchymal stem cell, which was never really meant to be there, doesn't have that capacity to slip through. So that's why MU cells were meant to travel in that method.

• 46:42Speaker 01

  So they, they're able to, size, regardless of size, they're able to slip down into a more narrow form and then slip through those capillaries.

• 46:50Dr. Darshan Shah?

  So this is another thing they have in common with macrophages, they can actually deform themselves to kind of slip under the door.

• 46:55Speaker 01

  That's right. And it would make sense. Cause me and you do have MU cells in us that we use in, in certain circumstances. And that's exactly how they would get to injuries.

• 47:05Dr. Darshan Shah?

  That's how they get there.

• 47:05Speaker 01

  You're right.

• 47:06Dr. Darshan Shah?

  Yeah, yeah. So, and you know, to further highlight this, if someone were to get IV MU cells versus IV mesenchymal cells, a much higher percentage of them would actually make their way systemically.

• 47:17Speaker 01

  Absolutely, yeah. There's a, the cascade of how things happen is you have an injury. Uh, it, there's cytokines released and there's chemokines.

• 47:25Dr. Darshan Shah?

  Yes.

• 47:26Speaker 01

  Chemokines are these signaling molecules that, once they reach a certain threshold, I think of this as like one of those dogs that follows a scent trail. If they reach a certain threshold, certain cells are alerted, like the firemen, and then they, the, the, alarm goes off, they slide down the poles and they all are out. It's S1P for MU cells, sphingocyanone phosphate. We've, uh, characterized this pathway. And MU cells, when that threshold rises, chemotaxis is the process by which they release and then they make their way to an injury.

• 47:58Dr. Darshan Shah?

  Got it, got it. Yeah, it's so incredibly interesting how, um, how they also travel throughout the body to me. It's just the.

• 48:05Speaker 01

  Right. It, it seems like magic.

• 48:07Dr. Darshan Shah?

  Yeah.

• 48:07Speaker 01

  When you watch it.

• 48:08Dr. Darshan Shah?

  It really does.

• 48:08Speaker 01

  Yeah.

• 48:09Dr. Darshan Shah?

  It's incredible what our human biology has developed. It just seems, it just seems unreal how complicated it is sometimes, but yet so, so elegant.

• 48:19Speaker 01

  Yeah, it's this, it really is intelligence happening. It's, it's, we just looked at them as back to med school. It was kind of, oh, the heart's breaking again. I'm like, the heart's so smart. Like it knows what it's doing. It's trying to do it. It's even adapting to its environment, pressures and valves and every, everything's adapting. So I look at these cells the same way. It's just miracle, the way they can search and find and through the labyrinth.

• 48:43Dr. Darshan Shah?

  Absolute miracle. And so let's talk about that. You know, you mentioned heart health, right? So one of the uses that I know they're studying in Florida is using stem cells actually regenerate cardiac tissue after a heart attack, a cardiovascular event, right? Where artery gets blocked, muscle tissue actually dies. And we all know that, you know, the muscle of the heart doesn't do a good job of regenerating itself. So then they utilize these cells intravenously to make their way to the heart and then regenerate dead cardiac tissue. They've actually done studies where they've done this with other types. And you're probably familiar with these studies where they've done them and they found better cardiac function. Tell us a little bit about potential applications around cardiovascular disease from mu cells and for just stem cells in general.

• 49:28Speaker 01

  Yeah, stem cells in general, the, the way to think of stem cells in general is if they're showing up on site, they're acting as like a mobile pharmacy. They're, they're not engrafting, they're not becoming that tissue, but they're acting as like an exosome signal producer. They're saying, you know, hey, do you need this? Do you need that? How can I help? They're producing a lot for that region, but any cell that does die, they, they're not going to replace that cell necessarily. And as mentioned, cardiac tissue is not that great at regenerating compared to other tissues. Whereas mu cells, which there are seven human trials out there, one of them being for, for mitocardial infarction or heart attack. And there's some great basic science studies on, particularly there's one on rabbits,

• 50:08Speaker 01

  where what they did is put a tracer on those mu cells and they see them make their way to the heart and actually engraft in that tissue. So everything's playing a bit of a role. That doesn't diminish the role of a regular stem cell. It's kind of the local police that's helping out as well. But also particularly mu cells, the unique factors that they're able to engraft. And, and the way they do that is actually a bit fascinating. They, they see a cell and they say, you know, is this guy too wounded or can he make it? If he can make it, they'll just help like a regular stem cell produce some factors and rejuvenate them. If they're not going to make it, what they do is they consume the genetic material of that cell. They look at which genes were switched on. And then that is the instructions of what they should become.

• 50:52Speaker 01

  So they'll see that cardiac genes were activated. Oh, I've got to become a cardiac myocyte and then they'll differentiate. And there's a few studies actually online where you can watch them in real time, consume that material. And then you see the, the fluorescence go off once they're expressing some of these cardiac genes.

• 51:09Dr. Darshan Shah?

  This is wild. It's like science fiction, you know? It's, this is mind blowing.

• 51:14Speaker 01

  Is, I think that's why there's been a slowness to adopt, adopt that this is possible.

• 51:20Dr. Darshan Shah?

  It seems unreal, right?

• 51:21Speaker 01

  It does. To me, if I step back and I just refresh what I understand, I think biologically it makes sense though, to have something like this.

• 51:29Dr. Darshan Shah?

  Sure.

• 51:29Speaker 01

  A small population available for this sort of catastrophic event.

• 51:33Dr. Darshan Shah?

  Yeah. But what's incredible though, is our ability now to harness these cells from fat and bone marrow, for example, or from an umbilical cord, from if you're not going to take them autologously, inject them intravenously and get them to where they're needed, right? It's, that's the part that is going to change medicine forever. Because if these are truly engrafting themselves and turning into new tissue, that's applicable to many other cell types, not just.

• 52:04Speaker 01

  Yes, absolutely.

• 52:05Dr. Darshan Shah?

  The part, right?

• 52:06Speaker 01

  Yeah, it's, that, that's a totally new ability. And I think it's important to look for uses right now. How can we apply them? How can we, you know, implement them? And I do want people to know, yes, we are continuing to push down clinical trial pathways. We're, we're trying to study as much as we can at once. And then there's just the basic science of, you know, how exactly are they doing that? Why are they able to do that? And how can, I think even IPSC research can, can take a little something from, for example, they express something called LET7 and LIN28, which is actually this brake system on pluripotency. It's holding pluripotency in check so that they're not over expressing pluripotency. And I wonder if even in an IPSC model, there's no brakes.

• 52:50Speaker 01

  You've turned on pluripotency, but without some of those checks, it's, it's less natural.

• 52:55Dr. Darshan Shah?

  That's interesting. Yeah. So you mentioned the cardiac trial. What other trials are you aware of that we should know about?

• 53:01Speaker 01

  Yes. So the, the, the strongest furthest trial in Japan was the subacute ischemic stroke trial. There was on about 35 patients, I believe. And, and there was a pretty strong signal in that trial. They're just looking for safety and it's a beginning, you know, phase two A, where we're looking at a little bit of efficacy. There are seven trials total, as mentioned, there's one on ALS. There's a pediatric hypoxic birth trial. There was a cervical spine trial. And there's a, there's a few other out there that we have a whole research hub online that people can dig into. There's somewhere between 100 and 150 papers total on them. So those human trials were fairly well done, safe in all of them, well tolerated in all of them.

• 53:44Speaker 01

  And now our goal is to transition some of that over to, to US trials.

• 53:49Dr. Darshan Shah?

  That's amazing. So I'm so excited about these mu cells. I just can't wait to see what comes out of these trials and potential applications way beyond just, maybe on joint injuries and joint degeneration. Sounds like, you know, this could be very helpful in treatment of many diseases as well. I mean, to have something that we can give people after a stroke or people suffering from ALS, these are previously untreatable kind of issues, right? I mean, we would struggle so hard with these poor people. And if this shows a positive signal, that's going to be a game changer.

• 54:23Speaker 01

  Yeah, there, there's a few points I, I kind of want to mention is, you know, we are, we, we've got a chance here. Sort of like we were talking about, and really the things that I think we're passionate at mu cell innovations about treating are a lot of things we don't have access to yet, like stroke. They're mostly inpatient and traditional hospitals. And, you know, the Florida law and some of these stem cell laws allow us to work in the longevity and orthopedic space. But the, the big indications are the ones you have to really push into the mainstream for. One factor I definitely want to highlight too, is this whole immune privilege that they exhibit as well. And because we had, we had talked about how some biologics are rejected though, like mesenchymal products do get attacked by the immune system.

• 55:06Speaker 01

  The biggest thing that opens the gate with mu cells is their ability to be immune privileged and accepted from, you know, one person to another.

• 55:15Dr. Darshan Shah?

  Right.

• 55:15Speaker 01

  When I came out of training, that was one of the biggest things I noticed was if you can't solve that problem, everything else almost doesn't matter because they're going to be rejected. And, and the examples we know of this are when a mother becomes pregnant, that, that placenta and that tissue is actually another, another being, right? That's a different genetic code. That's a different zip code, but that is tolerated by the mother. And that's actually a very fascinating fact. It's through this HLA G is this glycoprotein that's expressed that's kind of like a cloaking or it's like a universal passport to be accepted. There's this whole interesting, you had said this word earlier that I love, chimerism.

• 55:58Speaker 01

  And we know that the, the fetal tissue, the, the baby actually donate cells to the mother. And you can, you can sample tissue, they've now done this sample tissue of the mother and say she had a son. You can find XY or male tissue within the mother. So we know those babies are actually healing those mothers. But the thing I learned more recently is the mother is actually sending cells into the baby that stay after birth. Stem cells that exist after birth in the child and become activated in certain instances. And those cells also express HLA G. So there's a little bit of a question around, we now know that we're all chimeras. We all have our mother's cells in us.

• 56:42Speaker 01

  She has our cells in them. And then you have your grandmother, you have any siblings that were born before you are all actually. So when we think of the body as a country, we are actually made up of citizens from other people in our, our family as well.

• 56:58Dr. Darshan Shah?

  That's incredible.

• 56:59Speaker 01

  And that kind of opens the door is mu cells maybe aren't that different than, than some of those cells as well. They're, they're some source that can be transmitted from one person to another. You can, you can donate them. And there are systems within the body to tolerate cells that aren't necessarily your genetic material.

• 57:18Dr. Darshan Shah?

  Yeah, I did transplant surgery for a couple of years and, you know, the one thing that we were most concerned about was rejection, right? And so when I first started looking into stem cells myself, I'm like, why are these just not rejected? And I learned about HLA G. And it's just fascinating, you know? And now what you're telling me, this is some new information for me, that the mother's stem cells end up in the children as well. So that's like one more thing we get from our moms, because all of our mitochondrial tissue comes from our mother as well.

• 57:45Speaker 01

  That, that's right. It actually, yeah, the mitochondrial tissue, it actually gives me like a little bit of chills to think your mom, her, one of her last gifts to you is she gives you this embedded source of pluripotent cells that are, that are living and they activate on emergency. And, and so you do have this source within you of your mom's cells still.

• 58:04Dr. Darshan Shah?

  Yeah. So basically every bit of energy that you produce in your body comes from your mother. And also every bit of healing capacity is also passed down from your mother through the stem cells.

• 58:14Speaker 01

  She's looking out for you. She, she's looking out for you long-term.

• 58:17Dr. Darshan Shah?

  Mind blowing. It truly is like the gift of life, right? When you look at it at a biological cellular level as well, it's mind blowing. Let's talk a little bit about safety around these products. Because this is where, you know, they've gotten really, I would say, you know, I think you and I have both heard of bad actors in this space, giving people these stem cells and causing major problems, right? And so these major problems range from massive infections to people actually losing function of their nerves, all the way up to death, right? And so this, this has happened with stem cells in, in, you know, we, we hear about these happening in other countries, but also even in the United States.

• 58:59Dr. Darshan Shah?

  And so I think there's something that you and I both want to be very clear on is that this is not from the stem cell itself. It's from the chain of custody and how people are handling the product, right? And so I'd love you to dive in to that entire, you know, landmine filled.

• 59:16Speaker 01

  Totally. This is a big one. I, I actually break it down into. Three issues, really. There's, there's, marketing is kind of one. Marketing can be an issue. Like, for example, you could grab some water out of the sink and say, this is Muse. And there's really nothing stopping you from just saying, this is a Muse product. Who's, we're a little bit just out in the Wild West of, no one's checking claims to some extent. And I think that is one thing the FDA gets pretty upset with is bad claims. But, but also, it's not terribly regulated. So unfortunately, it falls on, well, you hope providers do their best and you hope patients do their best to try to educate themselves. But one is a bit of a marketing issue. Then there's a manufacturing part,

• 1:00:00Speaker 01

  which things can go wrong in manufacturing. Like we said before, this is why we stand by this Dezawa designation, Dezawa product is because it's been proven and tested, and that's what trials are based on. And that's how you have to go about things. Other people could take methods and create things. We don't know necessarily what they are, but we know, imagine how sensitive baking a cake is.

• 1:00:24Dr. Darshan Shah?

  Right.

• 1:00:24Speaker 01

  A little too much or a little too little baking soda can wreck the whole project. Now imagine you're working with a living product. It's, you know, at the best, at best, it might not work. You might create something completely funky. So that one freaks me out, I guess, is more of the thing. And then there's use, there's clinical use is kind of the last factor where things can go wrong. And that's where we do our best to educate when you don't have, you know, eventually it's just on label and everyone knows how to use something. Like everyone knows, use this much Tylenol, definitely don't use this much Tylenol. Like there's guidelines and studies to sort of work you along. We've seen some people say, this is a Muse cell product, but it's maybe 10% Muse

• 1:01:09Speaker 01

  cells. What we know in the literature is Muse cells won't function like Muse cells unless they're at a certain threshold, because the, say, anti-inflammatory properties of whatever else is in there is going to wipe out that scent trail that they require to home and to act properly. So it's not as simple as just, we increase the number and, and, and then just procedurally, doctors, clinicians, there's a responsibility to use a lot of discretion on patient selection and, and application. And that's very hard to, you know, stress me out a little bit, what people are doing out there. But I just encourage, you know, anyone on the provider side, listen, we're in it for the long game. Use a lot of discretion. That's why, you know, I love that we're connecting with Next

• 1:01:51Speaker 01

  Health, people that do it the right way, come up with protocols, just keep it safe and, and, and simple. So.

• 1:01:58Dr. Darshan Shah?

  Yeah. I'm gonna add a fifth caution to your list there, too, which is the transportation and the handling of the cells throughout, from where they're made to where they're going. The entire, that entire journey needs to be done with such high levels of care and responsibility, because you are, you are like shipping live biological tissue, right? And so that shipped in a solution that can potentially also keep other biological entities alive, like bacteria, viruses, fungi, that can also then grow. And if you're not very careful with the refrigeration or the freezing of the tissue all the way through that entire journey, and you give that to a patient, it can cause a severe infection, too.

• 1:02:41Speaker 01

  Yeah, absolutely. 100%. Yeah. And luckily, we're, we're working with a very top level lab in the United States. And so at least the manufacturing on the front end and the transportation is pretty well handled. But that is absolutely a factor of, and I've heard some, you know, unfortunate stories due to that, that sector.

• 1:02:59Dr. Darshan Shah?

  Right. And we have, you know, at our clinics, we also like, when we get the cells, we make sure that they're still at the right temperature, they're still, the dry ice is still there. We put them immediately into a special refrigerator that's made just for biological products, that we're always monitoring the temperature on 24/7. And, you know, we, we handle the procedures almost like we're doing surgery, right? Like it's very, you have to make sure you have sterile gloves on, et cetera. The whole chain of custody, it's so important with these products.

• 1:03:31Speaker 01

  Yes. That is where I still love, like our traditional medicine that we both come from, is when you've worked in an OR, like you know how it's supposed to be done from anesthesia. Anesthesia is kind of a crazy specialty, because you grab a drug out of a drawer, you draw it up and you administer it. So I do think.

• 1:03:47Dr. Darshan Shah?

  Drugs that can kill people.

• 1:03:48Speaker 01

  They can, they can kill people. And so there is like a, we respect the things that we're injecting and using, and surgeons respect what can go wrong as well. And I just would really caution, I hope everyone would follow suit. And I think that experience is really actually pretty invaluable.

• 1:04:05Dr. Darshan Shah?

  Yeah. I mean, to your point, you know, I'm a surgeon and I open many surgery centers and I really have done a deep dive into like, the level of regulatory oversight and just the, the rules and the, and the playbook that you have to follow to keep everything safe, right? Because the worst thing you could do at a surgery center is get like, people dying or tons of infections, et cetera, right? Like it has to be super clean and done with a really, real, with a really, I would say, level of care that supersedes even most other clinical settings. You'd probably agree, right?

• 1:04:39Speaker 01

  That's right, yeah.

• 1:04:39Dr. Darshan Shah?

  You have anesthesia and surgery there, medications that can kill people and you're cutting people open. And like, talk about the highest level of quality needs to be in these surgical centers. And that same mindset is what I brought to Next Health. It's like, we gotta run this like a surgery center. Like it has to be on point, perfect all the time, right?

• 1:04:57Speaker 01

  Oh, you can feel it when you walk into one. Yeah. It's, you know, when you learn that lesson, is when you're a med student and you walk a little too close to the, to the table and the scrub tech yells at you and then you're like, I'm never making this mistake again. And you understand like the reverence with which you handle products.

• 1:05:13Dr. Darshan Shah?

  Exactly, exactly. Yeah. It's, it's a, and it needs to be done, right? And this is what's going to keep this whole industry safe and, and make sure that we have the safety so we can then truly assess the efficacy, right? And so.

• 1:05:24Speaker 01

  Yes. Yeah, yeah. Now, I, I tell everyone, we're just pushing for Muse cell escape velocity is when we finally make it mainstream and into the, the hands of those people. I would love to see mainstream surgeons and, you know, rheumatologists and orthopedics and everyone using this in a typical clinical setting. And, and we're doing the best with what we're given right now. Yeah.

• 1:05:49Dr. Darshan Shah?

  Yeah, absolutely. And I think, you know, I think a lot of people might think that stem cells will eliminate the need for orthopedic surgery, for pain management. But I don't think it eliminates it. I think it contributes greatly to the success of it, right? Because, you know, as we know, there's an unlimited amount of surgery that needs to be done and people within pain that need relief and people that need orthopedic problems corrected. And it just keeps getting worse and worse. Like the number is not going down, right?

• 1:06:16Speaker 01

  Yeah, absolutely. Yeah.

• 1:06:17Dr. Darshan Shah?

  So we need more therapeutic applications.

• 1:06:20Speaker 01

  Actually, one of the, the population that we've seen, we actually, our CEO, when he was doing stem cell science, he had isolated, now he looks back and he says, those must have been Muse cells. Cause he noticed there was a stem cell population, out of all the stem cells that got exhausted, almost in everyone by, you know, 40 or so. They were going down quick. And the population that exhausted them the quickest, diabetics. They were gone extremely quickly, this stem cell population. And he thinks if he would have checked, those are probably Muse cells. But yeah, it is back to the interconnectedness. Once again, I think that becomes, that's a big ethos in our practice is, it's not just cells or miracles. It's, it's all an ecosystem of connectedness and you, you prep

• 1:07:02Speaker 01

  people and you treat. Sometimes the Muse cells are the treatment. Sometimes they're after the treatment and, you know, after surgery. I've actually looked at indications like that of pairing with surgeons. You do surgery, we run an infusion after. What do the results say? I, I mean, I find it to be pretty promising. Cause if you had to say, what is a catastrophic event? A surgery is pretty dramatic, right? And you might need an extra, we know that wound healing suffers from a lot of these chronic conditions and maybe you need a boost.

• 1:07:32Dr. Darshan Shah?

  Yeah, absolutely. Wow. This was an amazing education in this frontier of science, Muse cells, that I'm so glad that we were able to talk about this. And I'm so excited to see where this all ends up. And I really appreciate the work that you're doing to push this science forward. Not a lot of people are doing this and you've like kind of shifted your clinical practice away from doing a lot of clinical to help with the research and the advancement of the science. So, you know, I applaud you for making that, making that commitment to just helping people get better. This is awesome.

• 1:08:03Speaker 01

  No, I mean, I'm, I think I'm just optimistic. I think I'm just thankful for the opportunity. And I kind of feel like we're both born at a great time in medicine. There's just a lot of chance here. So every day is really exciting to wake up. I'm thankful. We have a great team. Oh, I wish you could be in on the MCI conversations. It is unbelievably positive and genuinely pushing for good. And we're just trying to get some elbow room and, and, you know, so I appreciate what you all are doing at Next Health. And thank you for having me on the podcast.

• 1:08:33Dr. Darshan Shah?

  That's, that's been amazing. So where can people learn more about the things that you're doing at MCI and learn more from you as well?

• 1:08:40Speaker 01

  Right. Muse Cell Innovations. We just got a new website up for clinicians. They can get in contact with us there about just the logistics, which jurisdictions, these are allowed within and everything that comes with incorporating Muse cells in your practice. Patients can find trusted clinics there. We do have some clinics that we partner with and, and like we were saying, we want to highlight the people we think are doing it right. So of course, you know, if Next Health is offering, you can bet they'll be up there and they're all over the place at this point. So wherever they can, we're happy to promote you all. Me personally, just on Instagram at Jeff Uygers, just like the name is spelled in the episode. And that's it.

• 1:09:19Dr. Darshan Shah?

  Amazing, man. Thank you so much for joining me today. And look forward to having you on again in a couple of years and maybe next year. And we could talk about how much progress has been made.

• 1:09:28Speaker 01

  That's right. I think we'll have a lot to talk about. It's moving fast.

• 1:09:30Dr. Darshan Shah?

  Awesome, man. Thank you so much.

• 1:09:35Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.