The Missing Conversation in Exosome Science with Andrew Ignatow and John Borja of Exocellure

0:00Ekta Yadav:Hey guys, welcome back to another episode of Skin Anarchy. This is a very, very special episode because as many of you know, we have talked extensively on this podcast about exosomes and a lot of the EV science that's now coming into skincare, also in just aesthetics overall. And I think this is a really interesting and important episode for this series of conversations we've been having on the show because this is the first brand I've come across that has truly made me kind of stop and re-look at this space as it's being applied to aesthetics. So I'm not going to tell you guys too much right now, but I want to really dive into the science in this episode.

0:33Ekta Yadav:So without further ado, please welcome John and Andrew from Exocellular. Welcome, guys. Hello. Appreciate you having us on. No, I'm very excited to have you both on. And I can't wait to have this nice, balanced exchange about where, John, you can really tell us the nitty gritty about the science of Exocellular. But Andrew, just to understand from your perspective about what this means for the current landscape of this type of technology, you know, in aesthetics. As you know, it's very much booming right now. So just to get started, Andrew, maybe you can get us started, like just to learn about the brand and the company and where all of this began, the vision.

1:04Yeah, absolutely. So I think one of the biggest distinctions for us is we did not start out as a skincare brand or looking to build, you know, the next big skincare platform. We really started with exocellular from the scientific side. And I promise I'm not going to say anything that John should be saying while we're on here today, but it really became about how do we bring the value and benefits and promise of exosomes into the shelf stable environment. And, you know, we made a pivot early on. We were actually looking more on the medical wound care side of things is initially where we were designing the product and the platform to go.

1:41And obviously with the regulatory landscape, we've made the shift into topical cosmetics. So we just launched in January. We are solely focused on exosomes. And in fact, we are just going to market first with our highest potency post-treatment serum only in the professional channel. And so we really want to build this out from a scientific credibility perspective first. So I've spent, just to quickly introduce myself, so I've spent the better part of the last 25 years really focused more on the brand consulting, innovation, and strategy work. And so as part of that, being in the agency world, I was CEO of one of the agencies inside of Omnicom.

2:18And so I spent years, whether it was building brands and strategy or innovation pipelines from, you know, the Pepsis, the Nestles, the Disneys of the world. And what was interesting for me is probably about six or seven years ago, I was working on a project on the future of anti-aging and longevity for skincare. And so that was my first introduction to even what exosomes were. But what excites me is how to translate something with scientific credibility into the market in a meaningful way. And I'm sure we'll get into this later where it's kind of the hype is way ahead of the science today in the exosome market.

2:53And so I think that gives us a really unique positioning to lean into the scientific credibility and not just marketing claims.

3:01Ekta Yadav:Absolutely. And I'm grateful for that introduction because I think it's really important for our listeners to understand that you guys are not coming from a space of let's make another skincare product. You know, and I think that's a really, really important distinction right now. And I'm not just saying this. I know for everyone listening, you guys have heard countless interviews we've done here, you know, on exosomes. It's that we are all talking about skincare, but then we never discuss where their true regenerative, the breadth of it is, you know what I mean? And aesthetics, especially. So with that said, John, I would love to have you give us this like intro to exosomes, you know, just to really make us understand what should we, obviously as consumers know, but what should we know as even professionals in this space?

3:42Ekta Yadav:Whether we're doctors, dermatologists, estheticians, whoever's listening to really understand the science of the nanoparticles. Hello. Well, exosomes, they are really a subpopulation of extracellular vesicles, specifically those of endosomal origin. The particle size, they range between 30 to 150 nanometers. So it's really, really small. And they're very distinct from microvesicles, which bud directly from the plasma membrane, which are released during cell death. EV is the scientifically correct umbrella term. And exosome is a specific subclass defined by biogenesis pathway. So it's not just size.

4:17And our position at exocellular is that we will characterize to the exosome subclass specifically using markers that confirm endosomal origin and not just particle size.

4:27Ekta Yadav:Yeah, that was wonderful. And for everyone listening, I want to dive deeper into that, if you don't mind. I mean, let's talk about a couple of these markers. I know that the data that exocellular has on the marketing end, right, in the very beginning phases of creating any product, you guys have very strong data there, you know, and it's very transparent. So I would love for you to get us started on understanding what are the markers as defined by myASA guidelines or that we should know about and what do they mean? As for the markers, there are three tetraspans that we are looking at. One is CD9, one is CD63, and one is CD81.

5:01These are the most widely used exosome identity markers, but they mean very different when it comes biologically. For example, CD63 is the most endosome-specific, and CD81 is enriched on exosomes versus other EVs and confirms membrane integrity. CD9 is more broadly expressed. For biogenesis confirmation, TSG101 and ALIX are more mechanistically informative. And as far as what we use most of the time, we use the CD81 marker, which is very involved in cell signaling. And its presence confirms membrane integrity and endosomal compartment association. And it's more exosome specific than CD9 alone.

5:41Our position is that CD81 positively is more specific to true exosomes than CD9 or size alone. It is, I think, the right marker to confirm.

5:50Ekta Yadav:Well, that's good to know. Yeah, because we do hear about all three of them, you know, especially when it comes to like mainstream media. Andrew, I'd love for you to chime in here a little bit about what were the difficulties, these, right, as a brand in terms of like seeing where the media is headed with like this information, how it's so hodgepodge right now and knowing what you guys know about your product that you've done your due diligence. Like what's the most difficult part for you from that business side of like where this industry is headed and like what we should know, you know, and be aware of when it comes to the science versus not.

6:18Yeah, I mean, that's the perfect question for where the market is right now. So I think it's a very easy translation to talk about how the hype has gotten ahead of the science And it became, you know, with the proliferation of exosomes through the lafalization and freeze drying capability, essentially opened it up. And we like to talk about that lafalization solved a logistics problem. It did not solve bringing exosomes to the market in the most viable way. And it's really tough. Like you walk into any aesthetics conference and I think the number of exosome brands probably doubles every conference.

6:52There's new products coming out all of the time. There's some a lot of liberties taken with terminology, right? We hear exosome inspired, exosome infused, exosome derived, and a lot of people just making all sorts of claims that are very specific to exosomes, not necessarily to what's being delivered at the moment of treatment. And so one for us in the market, the benefit is the high level education and awareness of exosomes has reached a pretty good mass right now. And that's generally the hardest part of launching a new brand into a world like this is people even understanding what are we bringing to the market?

7:25And so now we actually look at, we've seen the backlash in the market as studies have come out about liabilization, about other storage methodologies, even understanding frozen exosomes that as soon as you thaw them, they start to aggregate and clump and they may become useless. So we've really wanted to hit into the market. And this is why we chose to come in the professional channel first, because we want to bring this to plastic surgeons, to dermatologists, to high end medical estheticians and nurses that would understand why the benefits of the liposomal encapsulation that John will talk about, how that is the unlock to the stability from source to the moment.

8:01It's really about, and this is what I would push a lot of both clinicians, consumers, and even other brands. It is as important to identify the source and what we are starting with in exosomes. I think that is so vital right now because there is just a lot where people aren't even verifying what they started with. Equally as important, is it all there, viable, intact, and active at the moment you're going to use it? And we all know reconstitution, freeze-thaw cycles, all of these things are very damaging to the sensitive membranes of the exosomes. And so for us, leaning in with the science, leaning in with the breakthrough, I mean, we have two patents granted, two patents pending.

8:40We have really built this out. John and the rest of the team have done an amazing job of really enabling us from a market perspective to have the confidence to go out knowing that we may have the only viable exosome product in the shelf-stable environment. At the same time, we are also very transparent that we just launched in January. we have done a significant amount of testing. We know that the MyServe guidelines are evolving and what is it going to take and where the whole market goes. So our promise in the market is we won't shy away from any tests. If we haven't done it today, it just hasn't been in the roadmap.

9:12It has been to getting to this point where we know we have got something verified, independently backed by independent labs, that what we have built is real. And so it's very exciting for us. We can fight the headwinds in market because everything people are lashing back in the market is where we've come in from the beginning to solve it.

9:30Ekta Yadav:I love that. And I love everything that you said, because there's a really key point in all of that, that I really feel like we all need to really understand at this point as consumers and also professionals is that third party testing is everything. Making sure that from the very beginning, you do your due diligence on the research side, like the research guidelines side is very, very important in the EV space. For me, as a scientist looking into the space and the media that's been around it so far, I have been confused because we went from like not understanding to like hyper critique point.

9:59Ekta Yadav:I mean, that's a good thing. That's how science evolves. But at the same time, we're not discussing exactly what you just explained, Andrew, which is the first step is the professional space. How did we just skip over the, you know what I mean? Like, how did brands just skip over the professional outlet, let doctors, let derms, let estheticians use the products to figure out if they even work. And then let's worry about everything else. And that's what I've seen time and time again in so many companies that have come out with Exodome products is that you can't talk about the professional results, the clinical based results that they're seeing in an office setting.

10:30Ekta Yadav:So, I mean, that's my little rant about it. But I know for anyone listening, if you guys have seen those products, I know because it makes you wonder as a consumer, like, well, what is your data? Well, and I think because I could not agree more. And the flip side of that is so many XSM companies are putting out a ton of data. They're intundating us with a clinical study on this and something on this. But to your point, It's not answering the core questions. I agree with what you wrote here, but it doesn't answer your source. It doesn't answer your product viability at use. You know, that's the maneuvering.

10:59We'll put out a lot of data on the things that we can put, but we are focused on let's prove the things that are, let's get the data around the areas that prove what we know is already true.

11:09Ekta Yadav:That's right. No, I love that. No, John, I would love to pick your brain a little bit because Andrew brought up, I think, one of the most important parts of this conversation scientifically, which is the lipid membrane. You know, that you really, the case is an exosome. And I would love for you to do a deep dive for us if you can. And tell us about the relevance of that membrane and what we really do need to understand from the science side. Well, first and foremost, the lipid membrane of the exosomes, it's very fragile. The exosomes are supposed to be given out by the cell and immediately communicate with the cell right next to it.

11:40So there's this time in this ether is very short. The problem with a lot of the exosome products out there is that the creams and the serums and all these other types of vehicles that they're using is so damaging to that lipid bilayer. And the moment you put it in a cream or whatever fragrance they have in there, whatever preservative system they have in there, it ruptures the lipid bilayer. And what happens is that it releases all that information and it's gone and you end up with eczemers, which doesn't really do anything. And that's the beauty about having liposomal exosomes is that you have a liposome that's detecting the lipid bilayer of the exosomes in our products.

12:16Ekta Yadav:I want to take it a little bit, you know, a step further and ask, for example, Andrew, you brought up lyophilization. We've heard about lyophilization, John. It's been around since we started talking about exosomes in general. But then I think at this point as an industry, we know it's not a viable way to preserve exosomes, any EVs. What is it that we should really understand about lyophilization? Like if you were to explain like what that actually does to the lipid membrane and like, you know, why that matters, like how would you want us to understand that? So a couple of things. I'll give a little example here.

12:47You go to the wine store and you get yourself a nice good bottle of, I don't know, Pinot Grigio, right? You put it in the freezer because you want to make it nice and chilled, but you forget that you put it in there. The next day you open your freezer and the bottle exploded. It pops. You crack the bottle. Well, it's the same thing with liabilization. What happens is that when they freeze this, the internal pressure of the freezing exosome liquid expands and therefore it will actually rupture the lipid bilayer. And you're essentially lysing the exosome. And by freeze drying that, you also remove all the moisture that's required for all these very important components that's supposed to be working.

13:27But the problem is now you've killed it. You've pretty much attenuated everything. In addition, let's say, for example, you are successful in freeze-drying this exosome and it's still there. The moment you rehydrate that, and may it be saline or not, the influx of liquid going into the freeze-dried exosome is going to be so, so drastic. You end up still popping the balloon.

13:49Ekta Yadav:Yeah. So the misconception is that freeze-dried exosomes is equivalent to the liquid exosomes. Lyophilization is a preservation method, but it's not a neutral one. There's a study by Rogolska in 2024 directly demonstrated that lifelized mesenchymal stem cell exosomes, secretome, stored at room temperature, loses the majority of key bioactive molecules such as BDNF, BNGF, IL-6, and SV-CAM-1. The field adopted lifelization for logistical convenience, but it's not biological equivalence. The components are there. They're just all over the place. They're not compartmentalized into an exosome anymore.

14:29The way you described it is so helpful, which is why I love having John as our lead scientist, because he can help translate things for people like me. Yeah. I think a very easy analogy is we can freeze dry strawberries. Yeah. Right. You absolutely can. But when you rehydrate them, I think John just said, all the same things might be in there, but it sure doesn't look the same. It's soggy. You have changed the integrity of the structure, even if you kept a lot of the elements, which is why freeze drying is a very good preservation method for a lot of things. When we're talking about nanoparticle membrane integrity, just imagine what everything John just described.

15:04And I think now the data is there to show us that that is probably one of the most stressful things you can do to an exosome when you really cannot stress exosomes if you want them to work.

15:13Ekta Yadav:That's right. And I love that we are touching on this because as most biologists know, everybody who studied even biology 101 would know, is that if you are a membrane, a lipid membranes, mobility is not intact. It doesn't matter what's embedded in that membrane. So these tetraspanins that we always love citing, if you're freeze drying your membranes and they are not intact, you could have every CD marker in the world. It's not going to work because the membrane's not actually alive and working. So the fluidity of lipid membranes matters. And that is something that I'm so glad that we just talked about because in my opinion, that's the entire ethos behind the ability of these exosomes to even signal.

15:55Ekta Yadav:So with that in mind, John, I would love for us to take it a step further if we can. Well, actually, let's rewind a little bit because you talked about aggregation, right? Like, let's talk about the idea of aggregation of exosomes and talking about if you are freezing them, what happens to that aggregation component? And then why does that matter for us for the end product? Well, when you freeze the exosomes, like what I said, it really makes the lipid bilayer, the encapsulant, very brittle. I mean, that's such an extreme environment for the exosome to survive, right? And the moment you disrupt that, it's just going to lyse the exosomes and all those things will just go all over the place.

16:33But let's just say the exosomes are in a product, in a serum. If you don't have anything to separate those exosomes, keeping them apart, they're going to start clumping up like grapes. And the moment that happens, what happens to the lipid bilayer when a lipid bilayer hits a cell wall? Well, it will actually merge with it. And by doing that, what's that? And the cytosis, maybe the goodies inside the exosome is released into the other cell. But if you have a cluster of grapes with exosomes together, they'll start merging with each other and they're going to start getting bigger and bigger and bigger.

17:01And now you'll have, you know, a lot of proteins in there that will self-cancel out, you know, because you have proteins, you have an amine on one end and you have an acid on the other end, but you have another amino acid that's over here. So that acid now will react with the mean side of one amino acid, et cetera, et cetera. So now you're building a train and now that's completely attenuated and absolutely useless. So by making sure that you keep them separate by making liposomes to encapsulate these exosomes, you prevent them from actually clumping with each other. And I think an important distinction here too, because just like even the word exosome is being well overused in this space, we're starting to see the same thing with the use of encapsulation.

17:39I think what's really important and what John has described is that we isolate every individual exosome and then encapsulate each individual one. Even though I'm not a scientist, I've dug into a lot of patents and I've looked at how others talk about encapsulation. And I think that distinction, just because you encapsulate something, that doesn't mean you've protected it. Because encapsulating the whole package is very different than individually isolating and encapsulating each exosome. That is the core difference in our methodology, our patents, and why this is working. Because it's interesting, in the conversation that we see in the market, the aggregation conversation does not come up enough.

18:18Ekta Yadav:It never comes up, yeah. Rarely. In meetings, I would explain that to people or to doctors, and it makes perfect sense. But it's kind of a hidden piece that nobody wants to talk about because I haven't seen any other product out there that can address it. Yeah. And especially, John, what you said about the amino acid interactions. that piece that science never gets brought up like I honestly like that is incredibly eye-opening and I know for anyone listening that's really well versed in the space you guys know how important that is is that just because all of these vesicles have things inside of them doesn't mean that everything that's inside each of them is going to be compatible with each other so if they merge they're going to cancel each other's cargo out and it's not going to be what you think the true therapeutic value is not going to get delivered when they meet the cell so I mean I would love actually, for that to be a segue, John, if you can talk to us about the actual encapsulation, why do liposomes matter?

19:08Ekta Yadav:How does it work for exosomes, the encapsulation technology you guys are utilizing? Right. So we use a phospholipid. That's the same type of phospholipid that's used in the mRNA vaccine. Essentially, it's lecithin, and it's a very simple process, but very, very energy hungry. The first time we encapsulated exosomes, we used a machine that requires so much pressure. So from a liquid state and you pressurize that liquid into about 40 ,000, 50 ,000 PSI, and it comes into this very microscope, a very small nozzle, and it atomizes the liquid. The moment it atomizes the liquid, and of course, with the addition of the lecithin, the encapsulant, it forms these spheres that's around 108 to about 250 nanometers in size.

19:52That was the very first attempt that we used high pressure to make tiny nano-sized droplets to encapsulate our exosomes. But if you want to make this in large scale, like in production facilities, it's not a feasible method to do it because it can only do like 50 ml at a time. So like research purposes only. It's for research purposes. So I thought of other ways to actually make nano-sized particles. And I thought of using ultrasound. So I went to Amazon and I purchased me one of those jewelry cleaners that uses ultrasound. And I got my exosome liquid. I added my encapsulant. I stuck it in the jewelry cleaner, set it at the highest setting.

20:37I had to put some ice in the liquid because the sonic waves produces a lot of heat. And if you have too much heat, you kill the exosomes. And I just used sound to actually form the liposomes. And that in industry is used a lot. If they want to mix using ultrasound, they have machines that are 200 gallons that they can actually sonicate and produce emulsions and whatnot. But for us, we're using lecithin to make liposomes. So that's how we make ours now.