EXOSOMES: Everything You Need To Know About the Darling Molecules of the Anti-Aging Industry, With JuveXO's Brian Pla.

My name is Ben Greenfield, and on this episode of the Boundless Life Podcast, there are no stem cells and exosomes that are FDA approved for any indication.

The FDA considers them a drug. So right now, the only compliant way that they're being promoted is for topical cosmetic use. I use them a couple of ways. I don't know if you can see, I have a way better coif of hair than I did before. I did a hair transplant procedure. I came to Dr. Bauman and I said, look, we have a new formula that's just for hair. Do you think we could do a procedure? I'll be your guinea pig. After like 4 months, I saw him at another conference and he came over and he goes, I'm blown away. He goes, I had no doubt you were going to grow hair. I just didn't think you were going to grow it that fast. He goes, you've accelerated your hair growth process by months. And not only that, your hair texture has improved. It's almost like your hair got younger.

Welcome to the Boundless Life with me, your host, Ben Greenfield.

I'm a personal trainer, exercise physiologist, and nutritionist. And, I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

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Ben Greenfield: Well, I get a lot of questions. It seems like as many questions these days about these things called exosomes as I do about stem cells. They're like this newest, latest, hottest topic in the whole regenerative medicine and longevity field. I've never done a dedicated podcast all about exosomes. I've been looking around for somebody who could speak pretty intelligently, hopefully pretty intelligently, we'll find out, on the topic of exosomes. And, I met this guy at the American Academy of Anti-Aging Medicine. I know that's a mouthful, A4M, a conference in Vegas. He works with a company called JuveXO as in rejuvenation exosomes, I guess, J-U-V-E-X-O. And, his name is Bryan Plaw. He agreed to come on my podcast and fill us in on all things exosomes and answer all my stupid questions about exosomes because I've been injected with them, I've been infused with them. I feel incredible when I use exosomes. I even have nebulized them for my lungs, which I just did when I got back from a recent trip to India. So, I figured I'd have a chat with Bryan. So, Bryan, welcome.

Thank you so much, Ben. Thanks for having me. Awesome.

Yeah, for sure, man. How'd you get into this whole field?

Well, funny enough, actually, I'm not a medical practitioner or a scientist. I actually got into this business as a patient. So, about 12 years ago, a little more than 12 years ago, it was 2012. And the reason I remember is because Don Julio had just launched a new tequila brand and I had stem cell treatment in Mexico. And to celebrate, which is obviously not the best thing to do. We had a sample of that new tequila. That's kind of how I remember that. So, we were doing a stem cell treatment down there and Dr. Gonzalez who's really my mentor and really one of the pioneers in the space.

Wait, are you talking about Rafael Gonzalez?

That is correct, yes.

I've come across him before. A lot of people talk about him as being kind of the man in the regenerative medicine industry.

The Yoda. Yeah, the Yoda. So, he was doing a stem cell study down in Mexico, the bunch of MMA fighters to see a couple things. They're trying to see how well they recovered after a stem cell infusion. And then secondly, they were trying to see the effects of blood doping. I didn't know what a stem cell was at the time, but I, I was intrigued. And I went down there, had the stem cell treatment, and, and man, really felt amazing. I mean, granted, I was in my early 30s at the time, but nonetheless, it was— I felt it was a game changer. And it really started to set my path down into understanding more about regenerative medicine. And as I started to go down the path, about 18 months later, I asked, hey, is this something that I can do on my knee? And I had my knee injected. I had an old injury, had torn an ACL, was on the fast track to a knee replacement. My only option, hey, microfracture rehab surgery, none of the things that I wanted to do. So I said, well, look, I'm going to give this this stem cell stuff an opportunity. I got it injected and about 4 months later, I was playing basketball again full court with guys younger than me. I was like, "Well, this is something that works." And, that's it. I was off to the races. And, probably about a few years after that, I said I was turning 40, it was no longer about the money, it was about passion and purpose. And then, I founded a company based on cell therapy research and then subsequently, seeing what Rafael had done with these stem cells and the exosomes being an evolution of them, we started JuveXo. And that was fast forward 2019 and here we are today.

Ben Greenfield: When you got that knee rehab done, were you doing or the knee injection, was that just stem cells or was that stem cells with exosomes?

That was just at that time was just stem cells. This is over 10 years ago. So, it was just pure stem cells, and I'll get into that into the differences between the two in a bit. But, it was the pure stem cells.

Ben Greenfield: Okay. I would actually love to get into that. You a lot of times hear exosomes thrown around in the same phrase as stem cells. They're not the same, but can you explain what exosomes actually are and how they're different than stem cells?

Joseph Fung: Absolutely. So, exosomes are part of the communication that transpires between all cells and they include stem cells, right? So, the exosome is really key to making functional changes in your body to include and aiding in repairing and regeneration. And, they're really very, very small. They're tiny vesicles. They're actually measured in nanometers. So, they're about 30 to 150 nanometers in diameter and they're secreted by various types of cells. And, they're called extracellular vesicles. Why? Because they're not cellular. So, they're secreted by the cell and they're really taking that regenerative message from the stem cell and communicating it to the damaged cell to help it in the regeneration. So, they're just small membrane-bound structures that contain various bioactive molecules. I guess that's the best way. And they contain things like proteins, RNA, microRNA, but they're really messengers. If I could give you one piece of how to best describe them in one word is they facilitate communication, so they're messengers.

Ben Greenfield: So, a lot of people, I guess, thinking back to high school biology or whatever, when they hear about cells communicating, a lot of times there is some kind of a receptor on a cell surface, something is binding to that receptor and causing some kind of a chemical signaling cascade that causes a reaction to occur. Is it kind of like that with exosomes? Are they actually binding to a receptor on a cell or are they so small that they're literally going inside the cell.

Yeah, that's exactly— they're so small, they're able to penetrate, they've been able to penetrate the blood-brain barrier. And for a long time, exosomes were not even being considered, they were being considered cellular waste. Only as science continued to evolve and we got a chance to understand. In fact, so few people, I mean, and like you said, exosomes are being thrown around right now in terms of— and they become ubiquitous in the space, primarily in the cosmetic space. That how do you really know that there's an exosome in there? And we've even gone as far as we've taken images, live images of our exosomes in the product, which no one's been able to do in the field.

How do you take images of them?

Under electron microscopy. So, it's a very expensive component, equipment, sorry. I lost the magnifying, right? So, it's a microscope. So, it's meant to to really get the smallest types of images using kind of light and how they bounce off. So, we have some pretty amazing pictures that we're going to be releasing soon. In fact, at the AFRM when we met, you saw on the top we had, "Hey, we've shown you ours, now show us yours," because again, there's so many people making these claims. And, we'll get a little bit more, a little deeper into the science. And in terms of where exosomes come from, what's the process and how to differentiate. And so, I'll go into all of that.

Ben Greenfield: Yeah. It's funny that you bring up exosomes as being thought of for a long time as extracellular waste. And, this makes me feel old, but when I was taking exercise phys at University of Idaho, I remember my exercise phys professor, his name was Dennis Dolny, I remember a lecture that he gave where he showed these tiny little circles coming out of the cell and he says something like, "Yeah, this is the cell poop. This is just the waste that it discards after its metabolic processes." And, those were exosomes. He used the word exosomes, but 20 years later when some doctor is telling me he could give me an exosome infusion for some ungodly price, at least for me at the time, I'm like, "Wait, you're going to inject cell poop into me?" Yeah, yeah, no, it's—

I mean, it's, it's come a long way. The equipment has, has gotten better. You know, we understand the, the whole chemistry and biology of, of, of cells and all these nanoparticles and what's responsible for the entire cellular process. And what we're seeing is that when you have the stem cell, just the presence of the stem cell is not sufficient. It is, it is what are the— how are they communicating to the damaged cell to be able to, to do that? And, and the exosomes have been are that catalyst.

Yeah. So, how do you milk the exosome cow? Where do these things come from?

That's a good way to say it. That's the most polite way to say it. So, exosomes are created by cells as it pertains to— and as it pertains to our proprietary exosomes, they're derived from umbilical cord lining stem cells, which are more like a superior source of mesenchymal stem cells. So, we know that you hear the word mesenchymal stem cells People say MSCs, right? MSCs, correct. And these are ULSCs, which are umbilical cord lining stem cells, which again, because we've been in this space so long, we've tested every cell type. And we feel that these are the most— if you think what the umbilical cord is meant to do, the umbilical cord is meant to give life, 9 months carrying life. So, it is the most nutrient-rich environment. And, um, and, and that's, and that's where we find these cells. And so we call them superior MSCs in that front. And then exosomes are secreted from the stem cells.

Where else would folks normally get exosomes if it wasn't from the umbilical?

Uh, you know, exosomes are secreted by, by different types of cells. So, and then other, and other types of stem cells. So there's hematopoietic, there's endothelial progenitor. So there's different types of stem cells that producing exosomes. I could give you a cup of milk and there could be exosomes in there. And, when we get into that, you'll see that just having exosomes present is not sufficient. What really helps to contribute to the regenerative process is who are those exosomes coupled with, who are the teammates that are on the exosome team. And, that's why you're seeing the move from exosomes to secretomes which are in essence the cell secretions that include exosomes but other things like other proteins, amino acids, et cetera.

Ben Greenfield: When I've gotten exosomes, most of the time, even though— and I actually am curious about this, someone has given me a bottle of exosomes before that seem kind of stable at room temperature, you only got to keep them in the refrigerator, but usually they're frozen. And, when somebody injects you, they take them out and they kind of have you hold them in your hand or the practitioner holds them in their hand. Yeah, they hand thaw them. And then, there's a bottle and it's got the liquid in it that you then inject or infuse. But, is it just exosomes in that bottle?

Well, look, I can't speak for what other people are putting in their product because, again, because it's become so popular and being used more and more primarily in the cosmetic space, then everybody's come in and just say, "Hey, we have exosomes. Here's our little vial." But so few could actually really vet what's in there. So, it's so important. And kind of like in real estate, location, location, location. When it comes to stem cells and exosomes, source, source, source. Really understand what the source of the exosomes and the stem cells are. What testing has been done on this? I mean, for instance, for us, we purify our cell population, we grow them up in a proprietary formula, and we've studied the appropriate method to get them to secrete these secretomes, which like I said, it includes hyaluronic acid and collagen. Those are the top 2 ingredients in our body, right? So, we get this naturally secreted along with our exosomes, right? So, everyone's like, "Oh, we have the purest exosomes." Well, we're seeing that just having exosomes present is not sufficient. In fact, we've even found other things as we've continued to go deeper into what's in our product. These proteins that are called beta-defensins 2, and you're going to start to hear a lot more about this soon because cosmetic companies, cancer companies are starting to see the effects of beta-defensin because of their antibacterial and inflammation mitigation. So, we're going to start to see a lot more mention of that here soon. And, that's something that we naturally secrete. And again, you can't just add this to the product, you have to be able to know what you're doing in the cell culture to have it secrete accordingly.

Ben Greenfield: Is the one that you're making, this bottle of exosomes, which it sounds like has the secretome— you said secretomes, right?

Am I pronouncing that right?

Secretomes. And then, maybe in the future, these beta-defensins, is this a product that would need to be frozen?

Well, so we ship it frozen because it's the best way to maintain it long-term. But, because of the base and how, again, we've gotten the product to come to be, our product, even once thawed, is stable in a refrigerator for up to 120 days. And even at room temperature for 90 days. And, that's something that most people will tell you it's impossible. And, I'll say, "Yeah, it's impossible if your science hasn't evolved to that point." I'll give you the example. If tomorrow we find a race that is able to pass one star to the other, for us, it's impossible, but it's only because we haven't advanced to that point technology-wise. Same thing with us and our cell process. We've advanced to that process, so we are way ahead.

How do you use exosomes for yourself?

Well, it's very important to make the disclaimer that there are no stem cells and exosomes that are FDA-approved for any indication, right? Because the FDA considers them a drug. So, they're throwing the exosomes along with the stem cells in the same consideration. So, right now, the only compliant way that they're being promoted is for topical cosmetic use.

Yeah. And, by the way, that makes sense because I was just in India and I gave a talk there and there were some doctors there. One of the doctors runs a cosmetic beauty clinic and she comes up to me afterwards. She's like, "Hey, you want to swing in for an exosome facial tomorrow?" And, I was like, "Oh, sure. Why not?" So, I went in there and I got the exosomes. And, while she was doing microneedling, before the exosomes, we were chatting and I said, "Well, have you ever nebulized these? Do you inject them? Do you do infusion?" She's like, "No, no, no, we're only doing facials with them because apparently in India," it sounds like similar to the U.S., "that's the only way that you can use them." And, she said Korea is where a lot of these facial exosomes are coming from that are used in the cosmetic clinics.

Yeah. And Korea is really considered kind of the gold standard. No one takes their cosmetics more seriously. So, there's a link to if you have a product from Korea, by default, it's going to be, "Ooh." And, they have different regulatory components there. But, a lot of countries do follow the U.S.'s regulatory guidelines. So, you're limited in terms of what you can and can't do. Now, if you're doing it in terms of a study of some sort under physician supervision and it's consented, you could use it under, but again, you can't make any claims, it can't be used as a drug. So, it's extremely important that that is distinguished because you don't want to take all the good work that companies like ourselves are doing and then just because it's becoming sexy and selling and people making all sorts of— and then that's what damages the industry for others, right? And a lot of times you have one bad issue and then they're throwing everybody into the same. And what I can tell you is that we've been in this space for almost 20 years. We spend a lot of money on our R&D, millions and millions of dollars on our R&D. We have a pioneer in the space. We have a huge science team, a beautiful lab in California. We're working with the FDA in multiple clinical trials with our stem cells. And soon, we're going to have a clinical trial with our exosomes too actually for osteoarthritis.

Well, maybe I'm confused because I've gotten exosomes in the U.S. I've gotten IVs and I've gotten injections. Is that illegal? Is the person that gave that to me breaking the law?

Well, as per the FDA guideline, you cannot administer an exosome systemically. Because it is, in essence, considered a drug. Even when you're getting the infusion of vitamin C, there's a doctor that's technically signing or a mid-level practitioner that's signing off on that stating that you're okay to have that done. And I know a lot of times it makes it seem like it's super easy. I'm just going to go get an IV, but anything that's going intravenously has to be under medical supervision and And, if it's being used for an indication, if you're trying to treat something, then it has to be a drug. So, I'm not going to speak under the conditions that your practitioner did it. I'm sure you guys had discussed it. I don't know what his consents were like, but if he's making some claims that he was treating you for something with that IV, then that's where the—

Ben Greenfield: Okay. So, it's more about the semantics. It's like, "I'm going to give you exosomes for XYZ" would not be kosher or legal, but just like this seems kind of dumb, but if they would just say, "I'm just going to give you exosomes for no real defined good reason," that technically would be allowed.

Ben Greenfield: Well, I mean, again, allowed is if we're going strict interpretation just to make it simple is topical cosmetic use. And, if you look at everything that we're promoting, it is for that. And, a lot of times, and that's where I think initially the exosomes got added to to throw in the same category because so many people were promoting them IV, especially during the pandemic, et cetera. And, if you don't have a vetted product that's gone through the exhaustive— I mean, just to give you an idea, with the amount of testing that needs to happen before you're approving this to go that we were able to put it into a patient into a clinical trial, right? It has to go— and I'm talking about our stem cells. It has to go through exhaustive sourcing where we have to do viral testing. So we're testing from everything from CMV, EBV. I mean, those cytomegalovirus, Epstein-Barr, about 70-80% of the population has that. So any, any source that came back with that or any umbilical cord that we got with that was discarded, right? Then if it was positive for any sort of other infectious disease, discarded. We then do genetic testing to make sure that there's no genetic aberrations. If anything came back, that was discarded. So it's an exhaustive process to find a cell line. That you're able to work off of and why it's impossible. You can have all these people doing stem cells because that's extremely time-consuming and expensive. So I always caution people, really understand, you know, make sure your doctor is asking whatever company they're getting anything from, what is the source, what testing has been done, where is my certificate of analysis, so that your safety is first before any outcome.

That's actually really good to know because I think at least I get the impression that in the regenerative medicine and whatever you want to call it, the biohacking industry, people kind of think of exosomes as a lot safer than stem cells because stem cells seem like tissue. A lot of people say that you can get an immune response or flu-like reaction to stem cells. People's joints swell, they feel kind of lethargic afterwards, whereas it seems like the prevailing claim that a lot of people make is exosomes are just pure and clean and all they are these little vesicles, but it sounds like since they are derived from tissue, you have to be just as careful with them as you would need to be with stem cells.

Correct. Any cellular-derived product you have to be. And again, that is a narrative that's been spun by people that are selling it to minimize questioning around what homework they've done or what science they've done on their product.

Okay, so it's kind of the wild, wild west.

It's, it's been a bit of the wild west, but unfortunately, I think that, you know, the narrative is changing. Doctors are becoming more educated, um, and, and I think now, you know, with, uh, with New Maha Initiative, and I think we're gonna really start to see a, you know, push more towards these biologics and more companies stepping forward to invest the money to get get these products across the goal line for different indications, which is really what we want it to be. The second we get 1 or 2 stem cell products approved and then subsequently derivatives like exosomes, then, hey, so many people are going to be able to benefit because it's unquestionable the benefits you have on the immune system, inflammation, et cetera.

Ben Greenfield: When you and I were in Vegas, I literally got an email from a doctor about an exosome party. They were literally throwing an Exosome party where a bunch of people came into the hotel room and got their injections and their IV infusions. So, I don't know what kind of product they were using, but it is interesting how prevalent they are and perhaps how much more caution people might need to take based on what you're saying. But, you still didn't answer my question, dude. How do you use them?

I use them a couple of ways. First is I don't know if you can see, I have a way better coif of hair than I did before. So, I did a hair transplant procedure with Dr. Alan Bauman down here, one of the top guys in the country.

I've heard of him. He's like the GOAT for hair.

Yeah, exactly. So, I'm always making sure that anything I do, I have to try myself first. And, I know you're much the same, Ben. I know you guinea pig a lot of things over the years. You know, just it's important to have that first-person knowledge. So, you know, I came to Dr. Bauman and I said, look, we have a new formula that's just for hair. It's our, you know, our same Juvexo formula, but we've added a couple of proprietary recombinant proteins triggering, you know, hair growth in the follicle. Do you think we could do a procedure? I'll be your guinea pig. You know, we'll do this. And he was, you know, he laughed because he's getting sold to stuff all the time. He had used other Exosome products. And when— and, you know, after like 4 months, I saw him at another conference and he came over and he goes, he goes, I'm blown away. He goes, I had no doubt you were going to grow hair, right? And I, you know, and if you go on the website, you can see some of the before and afters and whatnot. But I just didn't think you were going to grow it that fast. He goes, you've accelerated your hair growth process by months. And not only that, your hair texture has improved. It's almost like your hair got younger, and to the point where I had a lot more white hair before and now my hair is dark. Again, we don't know why, I mean, but there's like— seems to be a catalyst component that if you're making the hair follicle younger to a degree, then we potentially are even maybe helping the, you know, melanocytes in hair, the pigmentation of the hair, right? Um, so I was extremely impressed, very happy, and that's what we knew that we have something special, and we launched the hair product line. And it's— I mean, we have tons of the really high-end practitioners across the country using this, complementing it either with a hair transplant or less invasive. So that's one. And the other one to use in combination with any aesthetic procedures. Uh, I've done— I've done it with, um, microneedling. I've done it with Morpheus, which is like a micro— an RF microneedling. All, again, to complement recovery and regeneration. So, there's a couple ways that I've used it.

Ben Greenfield: Yeah. And I'm sure there's a few bald dudes or women with receding hairlines driving in their cars right now maybe or listening in and wondering, "Okay, I'm ready. I want to order some exosomes." You can't just go to a website and order exosomes to your house and self-apply. These are for people who maybe aren't familiar with exosome protocols. You go to a doctor to do these, right?

Yeah, this is not— you can't find these on Amazon or, or at a— I don't know what— these are not to consumer because they still have to be, you know, driven by a procedure. Um, we have to also understand what the dosing is and what the frequency is, you know, when would you need to come back, um, and all that. And only a, you know, a licensed practitioner who understands what you're looking for and understands the product could do so. So we have practitioners all over the country, actually in many parts of the world, using our, our Exosome And, we've grown it truly organic. I mean, we haven't gone out there and promoted, we've just gone out and had some key practitioners using and it's grown organically driven primarily by the science, which is the way it should be.

Ben Greenfield: Yeah. I had the opportunity to have exosomes nebulized into my lungs when I got back a few weeks ago from a 2-week tour of India because my lungs were just blasted, man. I could only hold my breath for half the swimming pool and usually I can go down and back. I felt like I'd been smoking all day long. I couldn't take a deep breath without this weird pain and pressure in my chest. Maybe it was placebo. I don't think it was, but maybe you can tell me. The first time that I nebulized exosomes, and I actually did it 3 times when I got back from India, I felt within 20 minutes. Like I could breathe better. Do they act really quickly? And kind of as a second part of that question, what's going on? In the case of, let's say, damaged lungs, someone nebulizes, what are the exosomes actually doing to cause such a dramatic healing effect?

Well, if you think that intranasal delivery is— the nasal mucosa is very well-vascularized area, right? So, it provides a direct pathway to the bloodstream and even the central nervous system. Through the olfactory nerve and the trigeminal nerve pathways, right? So—

Oh, I didn't even think about the nervous system effect.

That's interesting. Yeah. So, unlike injections, right, intranasal delivery is obviously painless. It's non-invasive, way more patient-friendly. So, that's something that could improve on the compliance, especially for patients that are requiring repeated treatments. But, intranasal delivery allows for faster absorption. And it bypasses the digestive system. So, it's a more direct route into the bloodstream. And since you're targeting specific tissues, particularly in the upper respiratory area, which was the issues that you had, that's where things like if you have rhinosinusitis or other severe upper respiratory conditions, it's going to mitigate it better because you're getting right to quickly getting to that area in that proximity.

Yeah. It's my understanding they're attracting a host of growth factors to that area that rapidly accelerate healing.

Right. And, if you think that we have our product contains, it's very rich in high molecular weight hyaluronic acid and collagen. It's hypothetically triggering these respiratory benefits. Yeah.

Now, when you say intranasal, are you synonymizing that with nebulizing. The reason I ask is I actually have gotten— they're $6.99 on Amazon, these little atomizers, which you put one up one nostril, you draw whatever solution you're going to inject, you push it through the syringe, it atomizes that into very small particles. And, in the case of, let's say, a lot of people with mold issues these days, they'll do that with a peptide called VIP, vasoactive intestinal polypeptide, I think that stands for, and it has great effects. On the sinuses in terms of fixing mold issues in the sinuses. I've done that with exosomes and it feels like you're literally just putting a nootropic or a smart drug directly into your brain, but that's obviously different than breathing via mask and nebulizing. But, when you say intranasal, are you saying that even nebulizing you get a lot of intranasal delivery?

Yes, that is correct because what are you doing when you're breathing? You're coming in through your nose.

I kind of alternate. I do one deep breath through my nose and then out and then one deep breath through my mouth and then out.

Right. But, similar in that, of course, the direct atomize is obviously you're going just nasal and it's probably the most direct and more concentrated. Yeah.

What is the idea behind that and the effects on cognition? Have there been any studies looking into exosomes used as a sort of and not to use too street of a term but a smart drug?

You mean limitless?

Yeah, because I've done it before and you do feel kind of limitless.

If you know nootropics, right? So, nootropics is a growing space. You see a lot of peptides that are used like the C-Lancs, C-Maxes. There's cognitive benefits on that. We feel that for the same reasons, that it sounds like we should be able to have. And again, we haven't tested this, but just by the ingredients and the immune benefits that it should have. And again, it's a cumulative effort. And I'm not trying to be evasive, I'm just trying to pick my words carefully so it doesn't seem like I'm trying to sit here and sell this as a drug because I'm not. But I do want to show that of the potential benefits and why there's so much excitement in the space and why there should be continued investment in the exosome space to do things the right way because I think in cognitive function like Alzheimer's, Parkinson's, dementia, that's a very, very promising space. And, if we know now Alzheimer's is in essence it's a type of diabetes, diabetes type 3, Hey, what are we able to do if we're able to kind of bring down that systemic inflammation and we're able to help create new neurogenesis and angiogenesis? Are we able to improve that? And I'm hoping in time we can tell, but it is promising.

Ben Greenfield: Yeah. You're going to hate this story, but I have a friend who had chronic hip pain and inflammation and he happens to be pretty well connected and had access to a good source of exosomes that he had shipped to his house. And he pulled a bunch of syringes with the long, the pretty thin high-gauge needles into these syringes, laid them all out and got a massage. And, during the massage, kind of laid his leg out over his body to open up the hip surfaces and basically told his massage therapist to just plunge the needles and inject all over around his hips. And, he said he stood up and hasn't had any hip issues since. That's obviously not a recommended way to do exosome therapy. However, proceed with caution. The reason I bring this up is that a lot of doctors in a medical setting are injecting exosomes into joints. Is this very similar to a stem cell injection when done properly, not having your massage therapist cowboy it, but when you're at a medical clinic, is it kind of similar where they're doing an ultrasound, they're looking at the joint and they're kind of putting the needle in the right spot similar to stem cells, or is it more like peptides where you just got to inject close to the area where it hurts and you're good to go?

No. Well, I mean, I think it was the former, not the latter. And, if I asked you the question, what are the top, let's say, 2 ingredients, see, you'd love to have for anything joint-related, what would you tell me?

I'd say probably collagen and some type of an anti-inflammatory like a turmeric extract or ginger or something like that. That's what comes to mind for me.

Yeah. So, collagen, you're spot on. And then, the other one will be HA, hyaluronic acid, right?

Is that bioavailable though when consumed orally?

When consumed orally, No, but I'm saying you're seeing the HA used obviously topically, you're seeing it injected, you're seeing it— but those are the two ingredients you'd want to have. And, that's what our product is most abundant in. And again, not that we added to it, it's that it is secreted by our products. Back to the Secretrome being kind of sitting higher on the hierarchy than the exosome and the other ingredients, right? So, think of it this way, right? If I took Lionel Messi and I put him on a basketball court and I put a jersey on him, how well is he going to play soccer? Not too well, right? But, if I put him on a soccer field with a good team, the right equipment, and then I'm putting him in a position to win. And, that is the same thing. It's what who is accompanying these exosomes to the party for what they're trying to address. And in this case, we know what the answer is. In fact, one of the clinical studies that— or the first clinical study we're going to do with our exosomes for osteoarthritis, and we have a formula for that because how important HA, collagen, chondroitin sulfate, right? That's something you'll see in supplements as well, how well those work for the joint because it's generally delivered directly to the affected area. And, you're right, image guidance is so important that even the best injector is going to miss 30% of the time.

Yeah. It's a waste of money. You might get a little bit of effect, but in my opinion, it's a waste of money to get some kind of a joint injection without ultrasound-guided imaging.

Correct. So, and then once they're delivered to the joint, they initiate several key regenerative processes, right? One is promotion of cartilage regeneration, right? Growth factors carried by the exosomes, like for instance, not to get too scientific, but TGF, right, which is transforming growth factor beta, and VEGF, which is vascular endothelial growth factor, right? They can stimulate the repair and regeneration of damaged cartilage. Cartilage, right? They also carry a matrix which is MMPs and there are enzymes that break down damaged extracellular matrix and they help in remodeling that cartilage. Secondly, there's an anti-inflammatory benefit. So, usually, you'll get an inflammatory— inflammation first, right? And then, you'll get an anti-inflammatory event, right? So usually, as big as one is, the other will be. So, you want a good inflammatory response to have a good anti-inflammatory response. And, that's one of the things that's key to helping with joint issues, right? And, we have cytokines like IL-10, TGF-beta that they help reduce that inflammation in the joint, right?

Ben Greenfield: Yeah. I think that confuses a lot of people who kind of freak out if they go in for injection because a lot of times it's kind of of one step backwards to take two steps forwards because stuff swells. Sometimes you feel a little shitty. Like I mentioned earlier, you get flu-like symptoms in some cases with stem cells. There's this acute inflammatory cascade, which is also why it's a good idea to take a few really easy days after an injection or protocol like that and sometimes not load the joints heavily for up to a few weeks. But, the result then is a post-inflammatory anti-inflammatory rebound during which a lot of that healing takes place during the inflammation. But basically, people just need to be warned, sometimes you actually don't feel that great right away. It doesn't mean the physician messed up, it means your body is engaged in a healing process that's been reinitiated that should have taken place in the first place or maybe did but was ineffective. And so, just be forewarned if you're listening in. Some of these protocols, they they kind of suck for the first few days.

Yeah. And, I always tell people, I mean, look, even if you think of something as basic as PRP because there's growth factors, they're going to generate an inflammatory response. So, I always say, "Look, for the next 2, 3 days, you're going to hate me, but after that, you're going to love me." So, when it comes to the idea of exosomes and the longevity, Ben Greenfield.

I think it's been in the past year at the time of this recording that that big study came out in which they infused mice with exosomes. And via, I think, a mitochondrial signaling pathway, they saw— meaning like an increase in mitochondrial biogenesis and mitochondrial density— they saw, and I'm misremembering, it was something like somewhere between 13% and 17% increased lifespan in rodent models. With an exosome infusion. Did you see that?

Yeah, we see that. We see that all the time. But what I could tell you is that, look, it is possible that they could help save mitochondria. And as we know, the mitochondria is imperative in cellular function, right? That's why NAD works well, right? Because if you're not getting enough fuel from the cell, then all other issues come down. And ultimately, if you're looking at inflammaging down to the cellular dysfunction. So, if we're able to control that cellular response and increase blood flow, yes. However, only about 5% of studies done in mice translate. So, it's a very promising first sign, but you have to continue it to go from what you see in vitro to in animals.

Yeah. Dosing too, by the way. I have no clue the human equivalent. What if the human equivalent was 10 trillion exosomes, which is a little hard and expensive to hunt down?

Right. And, like I told you, but more important, and I think that the exosome narrative has been taken in the direction that more exosomes is better. And, that is true in secondary to what are the other ingredients. And you're going to hear me say this multiple times as I have throughout the podcast, is that the other ingredients that are there that are meant to help trigger the indications that it's meant for. Right. So just because I have exosomes present doesn't mean it's going to be optimal for osteoarthritis or optimal for a skin condition. It's what else are the exosomes there with, you know, who's in that party. And the HA, the collagen, all of these other present in combination with the exosomes, they combine, they make the music that we need for the intended indication.

Yeah. So, it's HA, collagen, secretosomes, you said beta-defensins.

We've even found glutathione in our product. We found biotin in our product.

Not because you put it there but because the umbilical tissue was expressing that?

That's it, the stem cells were expressing. That is correct. So, I would want to see other companies that are able to have done this amount of extensive studying so I can really know. It's kind of like if I started serving you food and I only gave you like, "Here are the top 3 ingredients, but the rest I just label it proprietary and you don't know what's in it." I need to know. I need to know what's served. We continue to push the envelope because— and that's where we're seeing things are starting to make a lot more sense. Why is it working so well for conditions like acne? Why is it working so well for hair growth? Because now as we're starting to find these other ingredients, it's like, wow. And none of it was added. None of it. It was all secreted. That's why we feel secretomes is the driver. And within the secretomes, exosomes are one of the components.

Yeah, you hear about let's say certain things that are good in some cases but in some people are contraindicated like high protein and a decent amount of carbohydrates support healthy physical activity, but those can also accelerate tumor growth if cancer is present. Or, NAD, like you mentioned, it has a longevity-enhancing effect but it's definitely contraindicated based on recent research in breast cancer patients. You can come up with a laundry list of items, but are there people who should avoid exosomes for whom research or otherwise has indicated it's not a good idea for these populations whether cancer or something else?

Well, I mean, look, anytime there's an active incidence of cancer, you don't want to take that risk, right? Just like if you're a pregnant woman or breastfeeding, rather steer clear of that. But, I would say Other than that, especially if we're talking about topical cosmetic uses, hair, there's no other contraindication. And in fact, the side effects are extremely mild.

Ben Greenfield: Have you ever seen studies that actually indicate exosomes could be helpful for chronic disease besides a musculoskeletal disorder like say arthritis or joint pain, which you've already established exosomes would be a good idea for? Have you seen anything related like heart disease, Alzheimer's, diabetes, anything like that?

In the context of autoimmune, and if you take a step from what, you know, kind of the studies we have ongoing with our stem cells and primarily what we're really— what we're targeting is aging and the immune system, right? So, I think we're really the only company that's going after this senescence, right? So, we're able to restore the immune system to a younger state. Really, we're starting at and we really feel that wiping out senescence, which is getting rid of these zombie cells or senescent cells. And so, if all of these conditions are attributable to aging, then by mitigating the immune system, you're able to make that better. And what I'm saying there is that We're seeing a massive, an epidemic, a real epidemic of autoimmune conditions across the board. And we could speculate as to the whys, right? We know there's a lot of whys, primarily the source, right? We know that we're being intoxicated every which way, uh, shape or form. So, you know, we have to navigate that field and be able to, yes, minimize the exposure to toxins so that we can minimize what it's doing to our body. Because even the best cellular therapy will not be able to overcome an overwhelming intoxication of the system, right?

Yeah.

Yeah. And I think that that's extremely— but with autoimmune conditions, I mean, RA, rheumatoid arthritis, we're, you know, we're in clinical trials for a study called the polymyositis and dermatomyositis or IIM. For short, right, which is an autoimmune condition, uh, you know, very rare but with no, with no cure. Most of these people have to get on corticosteroids for life, and we know what the, what the downsides of those corticosteroids in long term are, right? So, um, so if we're able to bring down the inflammation where you don't need that corticosteroid, right there I'm helping because, you know, all the other, all the other drugs you have to start taking on top of that because certain things start then stop working that we're seeing amazing results. In fact, we just got awarded a fast-track status at the parent group with our Phase 2, 3 now, which means we can get to a drug approval way faster.

Yeah, it's interesting. I have a podcast next week with a guy who claims to have developed certain herbal and plant-based ingredients that could improve your stem cell count or increase stem cell mobilization and health. It kind of makes you wonder how long it's going to be before the supplements industry has products that are something like, you know, whatever, Exosome Plus Plus or the Exosome Booster capsule or whatever. Did you think that's kind of coming down the pipeline?

See, now, if we're getting into plant exosomes and then we're moving a little bit further in terms of if it's just for the sake of having the exosomes, we still may be too premature in getting to that indication because we'll need to protect the exosome to assure that it could penetrate all the way through and get absorbed into the body in sufficient quantities to go after what we're trying to accomplish. And so usually anything that has to go through the digestive system is the least efficacious way to do so. I would love it. I mean, we'd all love to be a pill, a magic pill that you could take, right? And you get better stem cell proliferation, you bring down systemic inflammation, you can improve your A1c. Hey, we're getting there. I mean, if you see what the GLP-1s are doing, right? I mean, they— and there's— hey, there's— first you had semaglutide, then you have tirzepatide, now you have retatrutide, and we keep pushing and pushing. Because, hey, we're onto something. And we may see that that even in a microdosing component will have anti-aging longevity benefits because if you're able to really bring down A1c and sugar, the glucose in the body, you may minimize a lot of these other conditions. As we know, processed and processed sugar is a big problem. Cancer feeds off of that. So many things are fed, like we were saying, Alzheimer's is diabetes type 3. So, if we're able to bring down that A1C to a real low level and keep that in a homeostasis, is there a longevity benefit there? Maybe.

Ben Greenfield: I actually interviewed Dr. Tina Moore about the pleiotropic effects of small doses of GLP-1 agonist. And, I think you could definitely make a case for the system-wide effects that you're talking about when used in, I think, smaller doses than is being prescribed as a medical standard. Yeah, there's some definite positive effects. But with exosomes, you also hear about lifestyle practices that might increase, say, NAD, fermented foods or sauna or certain things that could even improve stem cell mobilization like high-intensity exercise or some people say things like hyperbaric oxygen. Are there lifestyle interventions that might allow for better activity of the exosomes that you've had infused or just a better ability of exosomes to communicate that you know of?

I think the first thing I'm going to go back to before anything you're doing post-treatment is what have I done pre-treatment. So, if we identify that there's any sort of major triggers, toxins, molds, glyphosate, adrenaline, plastics are now big. If we see that we have heavy metals, if we're able to see that we're systemically intoxicated with any one of these or a combination of them, then we have to first do our best to eliminate that source or greatly minimize it. Otherwise, you're putting in good money after bad money. And kind of like right now you have your headphones on, right? So, if you turn on the volume, How likely are you to hear any of the surrounding, anything going on around you? Probably not very well. Same thing. Now, if I take off those earphones, you're going to be able to hear everything around you. And that's the same concept here. We have to be able to let the cell breathe and take away this toxic environment so it's in an environment that it's happy so it could optimize. Because cellular dysfunction is the base of where everything starts to go wrong.

Ben Greenfield: Yeah, it's kind of the paradoxical nature of traveling internationally for stem cell infusions. It's very stressful on the body. And, I tell a lot of people, "Hey, if you can hang around for 3 or 4 days after your protocol and hunt down some hyperbaric oxygen and red light therapy and go outside and do some grounding and maybe a little bit of light swimming and some hot-cold therapy," do it rather than jumping right back on the plane into radiation and inflammation and disconnection from the surface of the planet right after you've put all those fragile baby cells into your body.

Yeah. And then, also before that, so prep your body as best you can so that it's going to be the best opportunity for it to succeed.

Yeah. If you go to BioReset Medical, one of my friends' clinics, Matt Cook who's been on the podcast in San Jose, He'll do stem cells, but the day before you do them, you're doing NAD, vitamin C, the ozone plasmapheresis, basically a full day of essentially cleaning up the body before you even move on to doing something like stem cells, which I think is a really good idea.

Yeah. And, he knows our exosomes well, he uses them. So, that's good. That's exactly right. That's a good protocol to follow. Then, I would think that that's the biggest thing that you could do more than anything that you could do after. Yes, you don't want to, like you said, you don't want to smoke, drink, all of those obvious factors you don't want to add. That's extremely important. So, that's why the diagnostics aspect is key, right? So, the more broader the diagnostics we have on the patient as they're trying to continue to improve. And, there's twofold, right? There's the people that are coming to you because they already have an autoimmune condition or some other condition that's chronic, right? That's, and that's one path you have to take. But then now, fortunately, we're starting to see that, you know, the younger generation is starting to become educated and surrounded by how important it is to be proactive and preventative with your health. And as the diagnostic tools improve, then we should be able to identify conditions way sooner and mitigate them. So, it's way easier to treat something in an early state. So, these advanced diagnostics, full-body MRIs, heart scans, et cetera, then, hey, now I'm able to put a more personalized protocol together which one of the components will be cellular therapy.

Ben Greenfield: Yeah, yeah. I just mentioned BioReset in San Jose. I love Matt. He has a great clinic there.

But, do you guys have—

do you personally have a Givexo clinic or a place where people go boots on the ground or are you just providing to physicians?

We sell primarily— yeah, we sell exclusively to the physicians. I happen to have a clinic that's— I have a center in Miami called Gentera Center for Precision Medicine. So, we're there in Coral Gables, Florida, and we incorporate all of these modalities.

What's it called? Gentera, like G-E-N-T-E-R-A?

G-E-N-T-E-R-A, correct. And, that was my first— I wanted to find a way to get cellular therapies into, so I started doing autologous stem cell treatments, hormone replacement, peptides, et cetera.

Oh, so you guys do this stuff at the clinic?

Yes.

Oh, okay. That's in Coral Gables?

Coral Gables, yep.

I should come say hi. I'll be in Miami next week.

Oh, definitely. And, in fact, we're working now with Prenuvo and we're sending a lot of patients over to them to get the full-body MRIs. We're seeing that it's the best technology right now for full-body diagnostics.

I've heard fantastic things about the Prenuvo. So, if a doctor is listening and they heard you say that you do need to be careful with your sourcing of exosomes, And, not that I want to turn this into a giant commercial or something, but if they wanted to try your exosomes or work with you guys, how's that work?

So, Juvexo.com is our website. So, all practitioners have to sign a practitioner use agreement. So, it's very simple agreement so they could read. And exactly, because we're educating the practitioner, we're showing them the science, we're giving them certificate of analysis, all the stability testing. So, you're walking in before you buy anything from us, you already know what you're getting.

Ben Greenfield: Bryan, this has been really interesting. I think my number one takeaway is just because of me being in the industry, I have people offer me products right and left. And, I think that I was under the impression that exosomes were way cleaner, generally safer, and offered a lot less risk because they were so simple. Compared to stem cells, but I've learned a lot on this podcast that now makes me think otherwise.

So, thank you. My pleasure. I mean, and even down to the feeding of the cells. And, I know there's so much talk about not having sugar. I'll finish with this thought, but our proprietary stem cell tech, we actually feed the cells a particular diet. And, guess what that diet is, Ben?

You feed the cells a particular diet? I don't know, pig slop?

It's a keto diet. So, they secrete the exosomes along with all this extracellular matrix that is meant for these cosmetic indications. So, look at even at the cellular level, we're giving them keto or no sugar. So, that's something that's extremely interesting. So, that goes to show how important it is, the entire process of how you're sourcing it. And, just because I give you a little brochure that says I have Infinity-1 exosomes, doesn't mean that I have the best product.

Yeah. So, probably also suggest don't do exosomes and stem cells and go eat a bunch of cotton candy. I'm generally a fan of carbohydrate mitigation to a certain extent within moderation for many reasons and sounds like there's another one here, your stem cell and your exosome health. So, that's super interesting. So yeah, the show notes are going to be at BenGreenfieldLife.com/ExosomePodcast. Sounds like the link if you're a provider or practitioners, juvexo.com/Ben. And, I'm Ben Greenfield along with Brian Plaw. And, this has been incredible, Brian. Thank you so much for sharing.

Thank you so much for having me on, and we'll see you soon, Ben.

Alright. Have an incredible week, everybody.

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