Revolution in Regenerative Medicine: Exosomes w/ Dr. Jordan Plews

Doreen Wu (00:00):
Welcome to Park Avenue Plastic Surgery Class, the podcast where we explore controversies and breaking issues in plastic surgery. I'm your co-host, Doreen Wu, a clinical assistant at Bass Plastic Surgery in New York City. I'm excited to be here with Dr. Lawrence Bass, Park Avenue plastic surgeon, educator and technology innovator. The title of today's episode is Revolution in Regenerative Medicine: Exosomes. Dr. Bass, we've talked about regenerative medicine before. Where are we going today?

Dr. Lawrence Bass (00:31):
You're right, Doreen. We have focused on regenerative medicine on a couple of episodes and mentioned it in several more. That's because it's seen as the future of the approach to treating many degenerative diseases and aging changes. I wanted to revisit the subject and what's happening with exosomes specifically. We've talked about some of the potential benefits, but also some of the regulatory hurdles with stem cells, but that's not the whole story. One hot emerging area right now is exosomes. What are they? How do they work? Why are they important? I've brought in expert scientists to discuss what's happening in this space. Dr. Jordan Plews is the CEO and Co-founder of ELEVAI Labs, which has developed advanced biologically active skincare for anti-aging. Dr. Plews studied stem cells and molecular biology in England and completed a PhD in the engineering doctorate program at University College London. He studied biochemical engineering and bioprocess management there, and he subsequently completed a postdoctoral fellowship and some business school training at Stanford University. He's conducted extensive research developing stem cell-based regenerative medicine solutions for a variety of degenerative diseases. More recently, he's focused his work on aesthetic medicine, and this summary of Dr. Plews' credentials doesn't really explain the experience and the history of his involvement with stem cells, but he's going to have the chance to explain that himself a little bit during this podcast episode. So Dr. Plews, welcome.

Dr. Jordan Plews (02:33):
Thank you for having me. It's a pleasure to be here.

Doreen Wu (02:35):
Welcome, Dr. Plews. We're very excited to have you on. So before we get to exosomes, can you review for us and give us an overview of the idea of regenerative medicine and its potential benefits?

Dr. Jordan Plews (02:47):
Yeah, so to me, the promise of regenerative medicine has always been about closing the gap between what I think we think of pharmaceuticals traditionally doing, which is often treating the symptoms with a pill or a drug to really focusing on what we can do to treat the problem at the cellular or molecular level to really repair what's going on. And so in my family, for example, my younger brother has type one diabetes, I have Alzheimer's that runs with my family. These are at the core, a cellular issue, and I think regenerative medicine has the opportunity to address these cellular issues in a way that we just haven't been able to with single molecule drugs.

Doreen Wu (03:31):
That's amazing. And Dr. Bass usually gives us a little bit of a history lesson when it comes to the subject we're discussing in the podcast. Can you tell us a bit about the history behind stem cells?

Dr. Jordan Plews (03:43):
Yeah, so there's a lot that has happened. I think the earliest I can think of is all the way back to the work of Gurdon in the sixties, and I ended up playing a role in my doctorate work, but I think stem cells really started to take off and get into the public eye in the early 2000s. You might remember Dolly the sheep was born as an initial clone, mammal clone in 1997, I think it was 1998, that James Thompson first isolated embryonic human embryonic stem cells. And then it was only a few short years later in 2001 that under Bush, a lot of that embryonic stem cell work was banned in the United States. Of course, before that, there was some early work on animal derived as inchy and embryonic, but I think it really got exciting, like say in those early 2000s where initially there was this sort of fear of like, wait a minute, we've got embryonic human stem cells. And I was lucky enough to be in the UK during that time where I was able to further the research where I think in the United States, it was a bit on pause until more work was done. And so this actually focused my doctorate on how can we make a cell that is equivalent to an embryonic stem cell without the use of embryos.

Doreen Wu (05:07):
Dr. Bass was planning on discussing exosomes in this episode. What are exosomes and what kind of role have they played in the story that you're telling about stem cell research?

Dr. Jordan Plews (05:18):
So at the most basic level, it's a message between cells. It's one cell sending another cell a message, and I think we have been trying to capture cellular messages in some form or fashion for decades. If we focus a little bit on aesthetics, I think we really want put youth in a bottle. That's what it comes back to, right? With exosomes, we have the opportunity to, on a cellular level, look at what the messages are and to some extent, potentially control those messages and provide them in a way that we have a little bit more say so. Where it relates to stem cells, for me, this really kind of, I go back into my past after biochemical engineering. I went to work at Pfizer as part of their bioprocess development group in England, this tiny town called Sandwich in Kent, and they have this big plant there. It's mainly making things for antiseptic during the war.

(06:24):
Kind of fun anecdote there. I learned while I was working there that mystery mystery was first an antiseptic and then it was a floor cleaner before it eventually became a mouthwash. So those of you've had the original flavor of Listerine might know what I'm talking about, and you'd probably go, yeah, yeah, that probably makes sense. Now it's all mint flavored. But when I grew up, it wasn't that way. But ultimately that whole situation led to me going, "we're treating the symptoms here, let's treat the problem." And when I got the opportunity to focus my doctorate on stem cell research, I did that. And it was like I say all about how do we create embryonic stem cells without using embryos? And that really starts with Dolly the sheep. So another little anecdote here. Do you know Dr. Bass where Dolly the sheep got her name from?

(07:15):
No, actually I don't. I always tell this story, I think it's kind of funny, but scientists, then they get the opportunity to name something. It's often something a little odd. My principal investigator and the UK for example, he loved the Battle of Trafalgar and Admiral Nelson. And so while there's a lot of TRA factors, which stands for tumor recognition antigen, he got the opportunity to name a few trough factors. But his TRA is for Trafalgar. And in the case of Dolly the sheep, she was cloned from a cell in the mammary gland. And so he chose a famous person who was known for her mammary glands to name the sheep after. So naturally Dolly Parton was the inspiration for Dolly the sheep, but the importance of Dolly the sheep was really that it's the first mammal that you're starting with a fully adult cell and you're going all the way back to an embryonic state and then going forward again, and before this, it was all on amphibians.

(08:20):
And so when I started my doctorate, it was like, okay, what does that guy do? And how can we reproduce that because we don't need to clone to benefit from the cloning technology. If I could take a bit of your skin, turn it back into an embryonic state, and then go forward into brain, kidney, liver, et cetera, you could basically be your own donor and you're in effect also aging yourselves in that process, which is exciting. So that's really where it started for me. And then when I moved over to Stanford, it was more about how do we translate that technology in different ways? And that's where I started working more broadly with other stem cell types and where it transitioned to exosomes. The kind of aha moment for me was we were, I should say, my lab in Stanford. I was under a principal investigator named Joe Wu. It was a heart lab, a cardiology lab in the radiology department. He's now head of the American Heart Association, but under them, lot of postdocs that were doing things like injecting stem cells into animal models, pig models, dog models, mouse models, things like that, looking at how did stem cells repair after injury. And so in a few of these cases, you inject the stem cells in into, say, the heart of a pig after a heart attack, and you see some benefit, but it wasn't clear what was coming from. You follow me?

Dr. Lawrence Bass (09:45):
Yes, I follow you so far. So the stem cells, there was some effect, but it's not clear that the stem cells themselves did it or how the repair got mediated, what the mechanism was.

Dr. Jordan Plews (10:02):
Exactly. And this is where it gets really interesting because I think most people understand stem cells as a type of cell that turns into other types of cells that differentiates. And while that's an interesting component of stem cells, I think what we've found in the last 15, 20 years is that they're signaling cells, that's a big part of what they do is they're receiving biological information and they're sending out information. And 15 years ago, people were saying things like pericrine factors, extracellular vesicles at best, most didn't even really fully understand, but it was through these experiments that we realized, okay, when you put the cells in, you're getting a benefit, but the cells are not sticking around, they're not turning into heart cells, they're not turning into a cell type that's fixing or the wound or the problem. So what are they doing? And that's where the aha moment was, Hey, these cells are releasing something and we need to dig into what that is. And ultimately, now we know that as exosomes.

Dr. Lawrence Bass (11:03):
So the exosomes were the signal that taught the existing cells how to repair. In the case of heart cells after a heart attack, what other kinds of messages can exosomes bring? What information is in the exosomes and how does that interact with the cells? What's been learned since then about how exosomes do the job and why they might be a more desirable target in all kinds of therapies, regenerative therapies compared to stem cells?

Dr. Jordan Plews (11:42):
Yeah, so I think a big part of this is around, we've sort of got to this point where we know stem cells are hugely influential in the body, that they play a distinct role in repair regeneration, but ultimately, you can't put cells in a bottle. And to some extent, if you go and inject them in, what you're kind of doing is putting the factory for these factors wherever you want it. But in many cases, you don't need the factory, you just want what it's producing. You want the exosomes. And so for me, it's more about, because we know almost all cells are releasing exosomes, all cells are participating in this messaging back and forth. The first question is really, why do I want a particular cell? Why do I want that cell's messages? And out of all of the messages it produces, what are the interesting ones? And so slowly but surely, that's the path we walk to get to the stem cells that we use and the exosomes we isolate, which I think broadly we're talking about exosomes today. It's one ingredient. It's one thing. It's a myriad of things really.

Doreen Wu (13:03):
Now I'm wondering what are the best exosomes and why is it that?

Dr. Jordan Plews (13:09):
Yeah, so for me, having worked with pretty much every major human stem cell type from embryonic and IPS cells to hemopoietic stem cells and mesenchymal, I've done a lot of work looking at the various types. And you don't generally want to mess with embryonics for ethical reasons. Same with fetal IPS cells are very interesting, but I don't think they're ready for prime time yet. Mesenchymal stem cells also known as mesenchymal, or I should say adult stem cell. These are ones that they're very have a proven safety record. These are the ones that exist in your body and are owning a lot of the repair and regeneration. And so that naturally was the place that I was drawn to in order to produce exosomes. But more than that, if you look at the common types, you get them from fat, you get 'em from bone marrow, they do exist all over the body, even around the edge of the iris in your eye. But if I had my choice, I always wanted to really go to these age zero stem cells. And so that's where we've gone after the Wharton's jelly, which is part of the umbilical cord, these Wharton's jelly mesenchymal stem cells. And that's because you're pulling them from a source that's not tainted by environment or diet or any of it with brains, right? It's arguably the youngest, purest source we can get.

Dr. Lawrence Bass (14:29):
And does that have to do with the actual message or the epigenetic associated information with those stem cells?

Dr. Jordan Plews (14:38):
Yeah, so that's a great question. I think we could do a whole episode probably on epigenetics, which I think we're finding is more and more important and is really underlying or underpinnings of aging. And we can affect our own epigenetics with our diet, our exercise, and things that we control. So in the context of aesthetics and stem cells, we're trying to take these age zero stem cells. And the real secret sauce is what happens in the lab where we are provoking or triggering them to release a message, an exosome message. And then of course, they're purifying that out. And I think talk about what's the best exosome. It's starting with the right cell treated in the right way to get the right message. And that's where it's a combination of the best cell type triggered in the right way. And then of course from there, it's about isolating the exosomes and preserving it in a way that's usable, which I think is its own challenge.

Dr. Lawrence Bass (15:40):
Okay. So maybe we'll have you back to talk about epigenetics and other day, but just to make the distinction clearer between what exosomes contain that this is message. So it's different from the individual proteins that the exosomes might hold the message for it's mRNA that codes for some kind of protein or some kind of cellular function. Can you clarify how that's different therapeutically than just dosing someone with the end protein?

Dr. Jordan Plews (16:17):
Yeah, sure. So to clarify, these exosomes, they've got a lipid bilayer. They've got RNA in there, and that can be in the form of mRNA, but it could also be in the form of micro RNA, which is really an emerging field still. And you can't have proteins, you can have proteins in there. Proteins of course, is an umbrella term that covers all the stuff that we usually talk about, enzymes, cytokines, growth factors. At its core, a protein is really just a chain of amino acids, but oftentimes those chain of amino acids are folded into something that is functional. And so I think as a point of reference, we are probably all familiar with growth factor products, but when you look at how growth factors are manufactured within the body, within your cells, it's not just about having the right chain of amino acids, it's about having it folded the right way with the right glycosylation pale on it, and basically you end up with something active.

(17:15):
And what I'm seeing out there, especially in the aesthetic world, it's a lot of products that are made by GMOs. They've taken a bacteria and then they've sliced in a piece of DNA to produce a growth factor. And then they don't tell you that, oh, by the way, the bacterial vector that's used, it doesn't have an endoplasmic reticulum, it doesn't have a gold golgi apparatus. So because of that, you have issues looks folding, you have issues with no glycosylation tail. It's literally missing some of the important things that are required to produce the protein in the same way that your cells look. And so the benefit of these exosomes is not only is what's inside of it produced properly, but it's going to be wrapped in this protective lipid bilayer. And as most people know, if you leave RNA or a growth factor out on the countertop, it is very unstable, but within the protection of the exosome, you can get stability in these unstable molecules. Does that make sense?

Dr. Lawrence Bass (18:15):
Yeah. So it's kind of like micro encapsulated, and it's not just the code for protein, but it's the biologically active form of the protein, or at least the information and the mechanics to produce that. Because if you have the protein, but it's not bioactive, it's not going to do much good. Now, I'm curious though how you think, because I'm old fashioned, the old fashioned medical training, you think about medications in terms of dose. How are exosomes dosed or how are they administered in a way that ensures that they have biological activity, that you're getting enough of them in a functional state, and how does that compare with how the body normally creates its own signaling using exosomes?

Dr. Jordan Plews (19:14):
Yeah, yeah. So to go back to what you're saying about micro encapsulation, I often refer to exosomes as nature's nano encapsulation. And so you have to remember, we're talking about things in this kind of like 30 to roughly 150 nanometer range, super, super small, less than one, 100th, the size of a cell. But dosage here is a tough one too, because this, it's not as though every single message that one cell sends another is of a specific dosage or not. I think what we're actually seeing is that as our bodies age, our stem cells are aging with us and the messages that they produce are decreasing with age as well. So it might start off that we're getting less of the message and then eventually we have no more of the message being produced at all. And of course, some of this is controlled by epigenetics.

(20:10):
I know in the aesthetic world, we often talk about collagen and how that degrades over time, how we go from the state of producing more collagen than we degrade to eventually degrading more collagen than we produce. And I think we can extend that model across biology here and say that that's likely what's happening with exosomes. And so the way I frame this is more to think about exosomes perhaps. Is it like a multivitamin? So when you take a multivitamin, your body takes what it needs and it discards what it doesn't. And I think right now the field often focused on what I deem a kind of American mindset. A bigger is better, more is better mindset with companies talking about number of exosomes as though that relates to dose. But if you are starting with two different cell types or two different labs, treat the same cell type differently, you can't compare those exosomes number to number, it's like dollars and pesos.

(21:10):
So when I think about dose, I think about really we're trying to give a more balanced message before we would try to give growth factors. And some people would say, I'll give you more, a bigger mix. But ultimately what we were trying to do with growth factors is take a part of that youthfulness message, a part of what young cells are expressing naturally, and to put that onto the skin. And I think what exosomes hold is a broader, more complete version of that message that then a more natural, better protected form. But at the end of the day, the skin is still a good barrier. A lot of what you put onto it is not going to get all the way to where it needs to. And this is why we've developed two products, both an in-office product that goes alongside the treatment and an at-home product so that again, you're taking this like a multivitamin, nudging your skin towards better health each day, rather than just overloading it with exosomes at one point in time, just like eating Thanksgiving dinner, you're still going to be hungry the next day. It doesn't make a lot of sense to just put the maximum possible at one point in time as much as it makes sense to use maybe a lower amount over a longer period of time. Does that make sense?

Dr. Lawrence Bass (22:25):
Yeah. And I think that's part of the reason why this approach is appealing compared to something like PRP where you have a whole harvesting process and you have to be medically administered to get it into the skin. You can't just lalde it on top of the skin and expect it to do anything, but you get that one shot at doing it and then you have to come back harvest process again to get more. To me, you have much more limited signaling because you are not getting that micro encapsulation, you're not getting the messaging to the cell to change. You're getting a single pulse of a number of growth factors, a number of chemotactic agents, that kind of thing. And so I think this is to my way of thinking as a clinician, a next step going forward that much more effectively communicates with the cells we're trying to reach in a way where the message is above the threshold of recognition. And I think that's part of the confusion that a lot of folks get into when they're thinking more is better. There's clearly a nudge to the cells that's going to be below what they might respond to, and it's probably easier to be below what they might respond to as our cells age. But once you've passed the threshold, then you sent the message and more doesn't necessarily make that message better.

Dr. Jordan Plews (24:11):
Exactly, exactly. And I have a slightly different view on PRP personally, I think about where does PRP stand in the spectrum of healing? And I think there's sort of the four stage model of healing that's pretty well accepted academically, starting with hemostasis moving into inflammation and eventually to remodel. And if you look at the cells that are involved in that, platelets are in the beginning phase. They're just right there at the hemostasis and the inflammation stage. They don't really play a role in the later stages, which are important for healing. And so when I think about looking at that, the stem cell actually plays a role across all four stages. And I think of platelets as sort of like they are part of the exosome story. So when you're pulling blood and you're preparing PRP, you're activating those platelets and there is exosome production by those platelets. So you have platelet derived exosomes essentially in there. But again, you're looking at what that patient is doing. So when you're pulling blood from that patient, how healthy is that patient? How much of their own biology has been impacted of an advanced age? Were they a smoker? Those sort of things.

(25:27):
So there is an exosome component to PRP in my opinion, but most of its job is to sort of signal the body to say, the damage is here, the damage is here. I've heard some use the analogy of that kind of Paul Revere. Others have kind of seen it as sort of the nine one one phone call. And that message ultimately is what's signaling to your stem cells to do the work, to come to the site where the damage is and send the signals or deliver the signals on how to proceed. But the problem is as we age, those stem cells are not getting better. We're not getting better at healing as we age. And by taking exosomes from these age zero stem cells, we have an opportunity to give back to remind yourselves how to be young again. And I think that's a powerful thing. And at the same time, it's arguably safer than some of the other approaches we've taken, which have been up to this point quite synthetics in my mind.

Dr. Lawrence Bass (26:28):
And I just feel like the breadth and the durability of the messaging is much greater than something like PRP

Dr. Jordan Plews (26:41):
For sure. Yeah, the number of factors by stem cells is much, much greater than what you're going to get from platelets. So the potential there is of course, higher.

Doreen Wu (26:50):
Speaking of the treatment process, Dr. Plews, can you tell us about some of the challenges you've encountered in harvesting exosomes?

Dr. Jordan Plews (26:58):
Oh, yeah. So there's a ton here, but this is really where I lean on my background in biochemical engineering. I think as a biochemical engineer, you're more or less trained on how to scale bioprocesses and how to eliminate inefficiencies. And so you'll find biochemical engineers usually working at pharmaceutical companies, but also many other places where filtration isolation and scale up occurs. So I've basically taken a biochemical engineering background and applied to it, the stem cell knowledge. And I think most people when they're taught how to grow stem cells, how to culture stem cells, they're taught to do them in a small dish because the reagents are usually quite expensive. So one of the major challenges here is that we've been able to grow stem cells at a large scale and therefore produce exosomes at a very large scale, rather cheaply. I don't want to say it's inexpensive because it's not but much cheaper than it was before.

(28:03):
And I think also in this regard, I can't help but mention that we don't use any animal components, and that's honestly a large driver of our cost. Because if you've ever worked in a lab anywhere in the world and you've grown cells, especially human cells, you've probably encountered something called fetal bovine serum or FBS, which is a nutrient rich derivative of cow blood or calf blood. But essentially, we don't need to use that anymore. It's a cheap alternative, but it carries with it some of the concerns of animals in general animal borne diseases. So when I was studying in the uk, we had to deal with mad cow. That still exists. It's also known as BSE, the prion based disease. You can't test for it. You can't filter it out. It can live in the cow for five years before they show any symptoms of it. So rather than take any risk there, we simply do not use any animal derived components or animal testing to get to our products. And I think that's important going forward. Most people don't want to buy an aesthetic product that has anything to do with animals anyways.

Dr. Lawrence Bass (29:09):
Right? It's just environmentally friendlier. It's ethically friendlier and potentially safer.

Dr. Jordan Plews (29:16):
Yeah. We also get higher consistency. Each lot of SBS is different, so we actually get higher consistency and safety, but it does cost us a lot more money. But in the end, I think it's something that everyone should be doing.

Doreen Wu (29:32):
Now, I'm guessing there must also be some challenges in the delivery of exosomes. Can you touch on some of those?

Dr. Jordan Plews (29:38):
Yeah. Honestly, the biggest challenge is to try to have people think about things a little differently. I think we've traditionally thought about the skin as this really great barrier, and not to say it isn't, but some people treat the skin as though it's a steel plate with holes drilled into it of a specific size. And the reality is that there's parts that are thinner and thicker, some that absorbs better than others. And when you look at the exosome, we're talking again, 30 to 150 nanometers. If you compare that to the width of an average sweat gland or an average hair follicle, we're talking about hundreds to thousands of times larger in diameter than the exosome. So exosomes are really throwing a marble down a well when you look at the natural porosity of the skin. So while I think there's benefits to doing things to open the skin up, whether that's microdermabrasion, microneedling, laser resurfacing, et cetera, we are seeing benefits that are just from topical application. And this may well be and is likely to be found to be true hair follicles, sweat glands, et cetera.

Dr. Lawrence Bass (30:53):
Now, I'm an aesthetic plastic surgeon, so I have to ask, just to be sure I'm clear, what are the specific types of biological activities that you think you're modulating with some of these exosomes? What things are we getting the cells to do? More like youthful skin and less like aging skin.

Dr. Jordan Plews (31:19):
So I think everything that we put onto the skin, regardless of what product it is, is having an impact on the skin. And so over time, we've found growth factors. We've found hyaluronic acid, that there's been more recent products, I think everyone's familiar with probably TNS Serum by Allergan, which is a fibroblast condition media product. To me, that's arguably the oldest exosome product on the market, right? There's probably not a lot of exosomes in there. They're probably not very well protected. But at the end of the day, we're talking about taking everything that those cells are releasing and putting it onto the skin rather than taking out of that mixture, focusing on the exosomes, which is what we're doing now. And so when you look at what you would expect to find in there, you can look at what these cells produce. So specifically with mesenchymal stem cells, they're producing an array of growth factors.

(32:16):
This is your fibroblast growth factor, keratin site growth factor, PGF, VEGF. There's about 20 or so I can name that, play a role in that. I think most people understand it's instinctively the benefits of growth factors. And I think the word growth factors is a bit of a misnomer. It's not always about growth. It's about healthy cell turnovers. But then there's also the usual suspects like collagen, elastin and other extracellular matrix proteins that we don't talk about as much like fibronectin and laminate. There's also really great antioxidants that are natural to our cells, such as SOD2. This is arguably much better than vitamin C. And this is produced naturally by the stem cell. The one that I think is most interesting is, I don't know if you're familiar with the work where they were looking at rodents, I think this was maybe over five years now, where they were taking old rodents and young rodents, and they put the blood from young rodents into older rodents and saw that the older rodents did better in mazes, did better with their skin and hair, their metabolism sped up.

(33:22):
They were just all around better. And oddly enough, when you put the old blood into the younger rodents, they age faster. And so if you follow that work through, there's a factor that's produced by mesenchymal stem cells called TIP two. And when that factor was removed, they no longer saw a lot of these benefits. So that may well be part of the driver here. And then I think what the obvious ones are things that are what you might call immunomodulatory factors, things like interleukins, interferons, we talked before the show here about interleukins and how that's developed over time. I think we all know instinctively in the world of aesthetics, at least that inflammation has its role. So it's not about shutting down inflammation actually, because we're causing controlled micro injuries with the expectation that the patient is going to heal up better than they were before. But you have to recognize as part of that process, we're expecting their body to do the work. And so all we're really doing here is supporting that, that natural recovery and repair, giving it a bit of a helping hand by giving it those messages, those reminders of how to be young to those older cells. So while those cells may not be able to write the message anymore, they can still read. Does that make sense?

Dr. Lawrence Bass (34:45):
It definitely does. It makes a lot of sense. And it's very much that this is a job that plastic surgeons have thought about for a long time. And part of the reason plastic surgeons have been involved in wound healing research is the notion of inflammation, good inflammation and bad inflammation. It's not that we just want to upregulate inflammation, and so we need to heal. We need to form scar to repair a wound or an injury, but there's a point beyond which that becomes dysfunctional. And in aesthetic applications in distinction to reconstructive ones hitting just the right balance point is critically important. And I've heard dermatopathologist talk about energy-based treatments and saying, "oh, you're just putting scar in the skin, stimulating neocollagenesis as a healing response." But that's an oversimplification, and it's really about the balance point, because more collagen in your skin is a good thing if you're old because you've lost a lot of collagen in your skin and it's not as well organized.

(36:01):
But simply putting an uncontrolled amount in without proper remodeling, which is that fourth stage of healing that you alluded to earlier, is going to be intrinsically problematic, and it's going to create, rather than create a beneficial aesthetic result, it's going to create something that we as plastic surgeons would need to come in and treat as a problem healing response. So that's really interesting. Now, I'd like to think for a minute about your products specifically, because I'm sure you could tell us many stories about the challenges you faced in developing them, but tell me what kind of problems you've overcome, what kind of attributes the products are able to deliver that distinguishes them from what's come before?

Dr. Jordan Plews (36:56):
Yeah. So before this, I think the idea was stem cells are great. I want them, I want to put them wherever I have damage. And unfortunately, most doctors today do not have a stem cell lab in the back room where they can prepare these fresh and put them into the patient. And of course, there's FDA limitations around that as well. What I think that stem cell exosomes potentially offer is a bit of that potential in something we can bottle, that we can put on the shelf we can use more easily. And a lot of people, I think, have a hard time with this because they're used to this idea that stem cells, when you want to preserve them, you got to throw them into cryopreservation. But you have to remember these exosomes, they're being produced right now in your body at 98.6 degrees. And if you look at the physics, which are controlled by an equation called coer equation, the smaller the diameter of the exosome, the stronger it actually is.

(37:55):
And so the idea that we can provide it in a room temperature formula actually makes a lot of sense when you look at it from that angle, more like an engineering mindset. So that's really the first approach is we saw that there were a lot of exome products coming to the market. Most of them were really designed for injection. The FDA has been very clear. You cannot inject these. And so this is why we've very purposely focused on topical applications and getting that formulation, topical formulation correct. And ultimately it makes the ease of use so much better for the of applications. And while I'm excited for a future in which there are some injectable exosome products, I think the road to get there is much longer. And this is a way that we can benefit from these today. And they're really just the kind of the next generation of growth factor products. So if you're familiar with our condition media, our growth market product today, this is that next generation on top that's that much better, not much more complete, really providing a more complete message of youth, if you will.

Doreen Wu (39:06):
Speaking of the future, what do you think is coming next? What is your vision? How will we be using exosomes going forward?

Dr. Jordan Plews (39:14):
Yeah, so it's an exciting future. I think there is a place for exosomes in a lot of different areas of medicine. I think injectables will take some time to get to where they need to, but people look at exosomes and a lot of doctors I talk to say, oh, this is new. It's unproven. But if you look on Google Scholar and just type in human stem cell exosomes, you'll get over a hundred thousand hits. And that's not even counting all of the papers that are about extracellular vesicles or are reassuring to exosomes using different wording. So I think we're a lot farther along and moving a lot faster than most people realize. And what's really interesting for me is I want to move from this place where right now we've been focused on what I would call the hero ingredient model, where a scientist extracts something from a plant or derives something synthetic like a chemical or puts together a peptide, and then they build this whole story telling you how it's going to do everything you need.

(40:22):
And at best, we have these products to have a handful of single molecules that do a few things very well. When in reality, if we just go back to the start and say, what is youthful skin doing? What's it producing? And how can we capture a more complete version of that message that leads you to exosomes, that leads you to stem cell exosomes that leads you to exosomes from very young skin? There's a variety of ways you can look at it, but arguably, we're getting that much closer to putting youthfulness in the bottle. And I think we're moving past a place where doctors were saying, oh, it's just lotions and potions. We can't really do anything. I got to cut to really get something done. I got to do something physical to get something done. I think we are moving past that now, where I hope that the benefits are clear here that when you put together the existing realm of aesthetic medicine with exosomes, there's so much more potential what we can do. And beyond aesthetics. I mean, we did have a whole nother episode on what other messages from other cell types in the body are capable of and how that's going to impact medicine. But again, if you pay attention to the story, it's growing in all. And I think we're going to be in a very different world in about 10 years time.

Doreen Wu (41:37):
That's very exciting. Lastly, before we end this podcast, Dr. Plews, can you share some takeaways with our listeners?

Dr. Jordan Plews (41:45):
Yeah, of course. So I think a lot of people are looking around going, how do I benefit from this technology? Today, our products, labs, products, we are only selling to dermatologists, plastic surgeons, and a handful of high-end medical spas. And really this is because this is a high education product. It's not something that's cheap to make or manufacture. And so we really are pushing it through folks that have the right expertise. But if you are a doctor and you're considering bringing these on, or you're a potential patient that wants to benefit from these, ask the tough questions. What is the source? What is the cell source of the exosomes? What, who's behind the process? Do you know anything about that lab or the person running that lab? How are they stabilizing packaging it? Is it really something that's designed for aesthetic topical use, or is it really something designed for injection?

(42:42):
And more than any of these things, I think for most users and users and doctors, they want know efficacy. They want to know that there's going to be real results. And so ask the tough questions. Look at the before and afters, look at the data. I think we're still in early days, so most of the exosome companies only have a few studies that are published. Some are ongoing. We have multiple studies and process right now. But I think, again, you want to at least make sure that you see some proof of efficacy. And again, always depend on your doctor, your dermatologist, your plastic surgeon, get their opinion before proceeding. Unfortunately, there is still a lot of misinformation out there, and we only get past it by asking the tough questions.

Doreen Wu (43:30):
What are your takeaways, Dr. Bass?

Dr. Lawrence Bass (43:32):
Well, I think Dr. Plews gave us a great summary there, but I'll just reiterate a few of the points. Exosomes teach youthful biology to aging cells. They deliver multiple messages. It's not just a single growth factor or a single, as he said, hero ingredient, and they signal the response in a more biological way, they're safe. And this is an advancement in what we're doing in skincare that's regulatory compliant. The right exosomes are really important. It's not that an exosome is an exosome is an exosome. So the notion of zero age stem cell exosomes seems to be a very important concept. And I will always agree, like most plastic surgeons will with what Dr. Plews said about data, everything is about outcome data. And there are very few skin products with any data about their efficacy. But some of the products do have efficacy data, and that's critically important to be assured that they're actually doing something meaningful. So exosomes are a big step forward in meeting the promise of regenerative approaches in medicine. And I'd like to thank Dr. Plews, the CEO and co-founder of ELEVAI Labs and stem cell researcher for sharing his fascinating view of the scientific advances that are changing our lives.

(45:14):
Thank you for having me. It's been a pleasure.

Doreen Wu (45:18):
I'll echo Dr. Bass, and say thank you to Dr. Plews for taking the time to come on and share with us your insight and expertise about this cutting-edge science. Thank you for listening to the Park Avenue Plastic Surgery Class podcast. Follow us on Apple Podcasts, write a review and share the show with your friends. Be sure to join us next time to avoid missing all the great content that's coming your way. If you want to contact us with comments or questions, we'd love to hear from you, send us an email at podcast@drbass.net or DM us on Instagram @drbassnyc.