The Truth About Regenerative Science in Skincare with Dr. Saranya Wyles of Mayo Clinic

0:00Hey guys, real quick. Have you checked out Droplet? It is by far the most revolutionary skincare device on the market. Basically, it takes those harder to penetrate ingredients and pushes them deeper into the skin layers. They're actually getting to the cells that can utilize those ingredients. Recently, they just launched their ExoSum Mist, which is a phenomenal product because it's using real exosomes that are shipped to you on ice. So you don't have to worry about them being degraded by the time you use them. And so when you put the capsule of exosomes into your Droplet device, it creates a fine mist.

0:25That mist is allowing those exosomes to be pushed into the layers where they're going to actually be able to interact with the cells. that can use them for signaling. If you want to check out the device, go to droplet.io, use our code ANARCHY, A-N-A-R-C-H-Y, to get a very special bundle deal on this exosome and droplet device duo. Hey guys, welcome back to Skin Anarchy. This is a very special episode, and I am truly honored to host our guest today. She is a trailblazer in the regenerative medicine space, a true expert, and I am really, really excited because as many of you know, I've been And, you know, wanting to bring this to you guys for so many years at this point, where we can get a real understanding of what does regenerative medicine mean in the context of skincare and aesthetics and how should we be thinking about it, you know, from obviously the consumer standpoint, but also for those of you who want to dive deeper into the science, you know, how to kind of frame your mindsets around it.

1:15So without further ado, please welcome Dr. Sernia Wiles, who is leading the charge at Mayo Clinic. So welcome, Dr. Wiles. I'm so honored to host you. Thanks, Ekta. It's an honor to be here. Yeah, I can't wait to dive in. And you have such an amazing, amazing background in medicine. I mean, you're an MD-PhD. You've got one leg in research, the other leg in clinical medicine. I mean, it's such a rare find to come across as an expert such as yourself. And so I'd love to kind of start there and walk us down memory lane. Like what got you into medicine to begin with? Yeah. So I grew up in a family of physicians and scientists.

1:52So it really, I would say it's dinner table conversations. Growing up in India, my dad, who's a pathologist, would have us talk about the cardinal signs of inflammation in Latin. So thinking about signs, my sister and I would come up with songs like rubor, color, tumor, dollar, punctualasa. So it was a very different, nerdy kind of dinner table conversation. But it was fun. My mother was a scientist and she would take me and my sister to the lab on evenings or weekends. And I grew up pipetting water. And so in a lot of ways, the lab and medical field and pathology was kind of home to me, was familiarity.

2:33So as I kind of grew into the fields of science and through science colors in high school and in college and explored the area of neuroscience. I also studied art history because I was very fascinated by the connection of science and art and how they interplay, but also just the beauty within our creative capacity. And during this time, I really thought about regenerative medicine as a sci-fi kind of magical specialty. The idea that we can heal from within that we had stem cells that could repair, rejuvenate, regenerate, and that these just seemed to be like these very magical field of research.

3:18You know, we, when I graduated college, the field of induced pluripotent stem cells had just taken off. Dr. Shinya Yamanaka in Japan was poised to, on his way to win the Nobel prize soon after that. And a lot of the science was really magical. The fact that you could take skin fibroblasts and reprogram and turn their clocks back in time and make them into pluripotent stem cells and then get those stem cells to become cardiomyocytes or neurons or even back to skin cells was really fascinating. So to me, it's just, I just kind of followed the magic, I think, and found my way to dermatology. That's amazing.

3:59I love that. I I love that you grew up in that environment and like it really shaped like your interest. I feel like I never hear that. You know, I always ask whenever I'm hosting doctors, I always ask that question of like, what got you into medicine? Because it's so interesting to learn, right? Like where did it start that just like wanting to discover science, wanting to understand science. And I just, that's fascinating. And I want to go deeper because now I feel like when we think about regenerative medicine, this is what I hear all the time. We talk about stem cells, and that's kind of where people stop.

4:31And I feel like there needs to be so much clarity. And so I'd love to start there. If you could kind of give us an understanding of what is regenerative medicine and what should we be knowing from the get-go as like the baseline of this field? Yeah, absolutely. So regenerative medicine is a field that we've been fascinated with since Greek mythology and even dating back further than that. It's the idea that our bodies can heal from within. It's the idea that if we think about Greek mythology, the stories like Prometheus who stole fire from Zeus and he was banished to punishment. And his punishment was that Zeus's eagle would come and peck at his liver.

5:14And night after night, that liver would regenerate and regrow and it would happen again. So it's this concept that our bodies could fully recapitulate lost damage function, and structure. So the way I define regenerative medicine is our innate ability. So heal from within, our innate capacity to regenerate, renew, repair, heal, and restore form and function. So it's not just structure, but it's that functional capacity that we're seeking. And this can be really defined broadly. Like if we were to think about true regenerative medicine in its nature. It's the idea of scarless healing. So it's the idea that we can replace and renew without fibrosis.

6:00We basically have healing back to that native structure and function, which is really hard to achieve outside the in utero environment. Once we escape the wound, there's really fibrosis that we're fighting with injury and a lot of other sequelae. But that's what I think our holy grail true regeneration still tends to be, and that's a mark that we're striving for. But until that day, what we have right now, I mean, sure, it starts within stem cells, but there's a lot of other regenerative tools that we are utilizing, and now more commonly the acellular toolkit within exosomes. But the goal of all these different products remains to try to renew that structure and function.

6:45That's very fascinating. And it's interesting how you frame that because I don't think that's how it's being portrayed. That's why I asked you. And I think that's important to understand because we have seen so much come out of like wound healing research, for example, right? And I see this happen so much in various industries where we're taking from regenerative medicine, but then we're not providing a context of like what that means for entire organs. So like skin is obviously the big clearing example, but But even when you look at other biologics that are being supplements that people are using or injectables, people are injecting themselves with peptides, I feel like there's no baseline understanding of what is actual regeneration of the body?

7:30What does that even mean? And so I think that's very fascinating. If someone asks you, give me your five top things that come to mind when it comes to true regenerative potential, whatever it is that the body is making, what would those things be that the body utilizes intrinsically to repair itself? Yeah, great question. So I think we can think about things like starting from surgical repair. So if we even just take a big step back of what's in our toolkit, it's grafting. That's where regenerative medicine started. So we borrowed from Pater to PayPal this idea that if we needed to replace the skin, truly we have to graft from other sites of the body and then use that to transplant that skin into a new area, like in most micrographic surgery or other facial plastics reconstruction for grafting tissues.

8:23So that is where we started with that concept that we can use our own tissues that have regenerative potential like skin and like other organ systems that could be used in a grafting capacity. And then we sort of moved into thinking about wound healing. You can look at matrices or substances that can replace and try to heal that wound. So extracellular matrix scaffolds or keratinocyte sheets were born to try to help patients suffering from wounds and burns. So those types of cellular alternates or extracellular matrix scaffolds really came into the wound care space that I would categorize in that regenerative bucket too.

9:08And then we started to move towards more of products that are used in our clinics like platelet-rich plasma, platelet-rich fibrin, growth factor technology. So a lot of them are either human recombinant or human derived. they're from the patient back to the patient so those are still being studied in some context or another and most of what i'm talking about today is in dermatology because that's what we're practicing and then there's stem cells so there's lots of different types of stem cells so mesenchymal stem cells embryonic stem cells induced pluripotent stem cells some of them can be used for clinical trials and therapy some of them you cannot if you have stem cells with that pluripotent capacity then they also have the risk of teratoma formation.

9:56So it's not ideal to use pluripotent stem cells, but multipotent stem cells like mesenchymal stem cells do have that capacity for regeneration and healing. And then the newer classes of treatment within the regenerative portfolio includes exosomes and peptides. Polynucleotides more or less have some capacity. I also kind of think about gene editing, like CRISPR-Cas9 technology, anything that can kind of optimize and enhance that structure function component could be characterized there. Exosomes are very variable. Very simply put, I talk about them as cell talk. This is how cells communicate with each other.

10:38We've known about them for decades, but really disregarded them as cell waste. But now we know that depending on the source, like if it's coming from a platelets or certain types of stem cells, then you can see it having regenerative capacity. So there are a lot of different tools within that regenerative toolkit, but I think how it's being utilized is really variable if it's autologous or allogeneic sourcing. That's, yeah. And I'm so glad you mentioned that. I was actually going to be one of my next questions for you is really kind of understanding exosomes because I've heard so many things, right?

11:15And I think as scientists, we do have to look at and weigh all of the information, all the data, but there is a lot of misinformation from what I've seen going around about exosomes, you know, in both ways. And I think I would love to get some sort of like a framework if you could provide some, because just a baseline understanding of like what can we expect from exosomes when they're being utilized for any kind of regenerative work, whether it's topical use. Obviously, we can't inject them, not allowed. The FDA hasn't approved that. But just from understanding the basics, what can we really understand?

11:50What should we understand about exosomes when they're being used outside of the lab? Yeah. And I think with the space of exosomes, especially in aesthetics, what has happened is we've put the cart in front of the horse a little bit. It's really gotten to be that the marketing has advanced so much further. If we could redo the playbook, what I think we should do is to reclassify exosomes into the word extracellular vesicles. So most marketed exosomes are extracellular vesicles. And I would say that's true for about 90 % of the products out there. To be a true exosomes are a very specific characterization that you need to hit and satisfy.

12:36exosomes have surface markers called tetraspanins, and those need to be shown as present. Exosomes have very specific size, but there could be some variability there. So it's not necessarily size only dependent. There's other ways that you can detect exosomes. So there's considerable variability. But before we even talk about that, I want to just share how much details that go into exosome production. And then that will kind of clarify why there's so much variability. The first step is the source. There's so many different types of sources. So there's platelets, stem cells, plant, some are claiming cancer, inflammation.

13:17So there's a lot of different cells that make exosomes. In some ways, exosomes are just messages, right? And so you can have spam or bad messages that you can get, and you can have good messages or positive signals. In fact, I think the way to do this is to reframe exosomes into therapeutics and diagnostics. So you can actually measure exosomes in your blood and do cancer staging. So certain types of cancer cells and metastasis can release exosomes too. And I say this because there's variability in the source level, number one. Second is there's variability in isolation. So So say you do decide to pick your favorite regenerative source, and then you decide to produce exosomes from that source.

14:00You have to think about how the, how is very different. So you can just like you would think about making coffee, you know, there's pour over there's filtered, there's espresso, there's a latte, there's very different cold brew. There's a lot of different ways to make coffee, right? So just like that, there's a lot of different ways to make and isolate that exosome. So some of them is like comparing apples to oranges. It's really hard to compare between the different sourced products because there's also differences in production. And then the third layer of variability is differences in detection.

14:36So not only is it how you make them, it's how you test it once you have it. So looking for tetraspanin's markers is one, you can do things like particle tracking. There's also ELISA and Western blot. So all these different ways to identify the protein is there, the exosomes there. And so we're actually working on a global consensus survey right now on topical exosome products. And we're trying to get survey from over a hundred different experts from around the world so that we can try to get on the same page as what we agree and disagree on for where this exosome category should be classified as.

15:16And like I said in the beginning, the key term would be extracellular vesicles. If we can go back and reclassify, it's really a lot of different signals that these cells communicate. So to get a pure population of exosomes, it's quite hard. Yeah. Thank you so much for diving into that. That's incredibly, incredibly enlightening. and what really came to mind was like people often cite mice from 2018 to 2023 and one of the things you brought up were the tetraspanins but then no one talks about mice also says you need to look at the cytoplasmic markers and then also look at golgi and you know certain organella markers and like we have to understand if they're there i mean these are just topics that i never see come up but then we like you said we put the cart before the horse and we now it almost feels like we don't know how to backtrack.

16:09That's what I see a lot of with brands, right? So with that in mind, I mean, for consumers that are buying these, do you think there's some sort of a risk associated with buying exosomes? I mean, like what is just your opinion on that? Like exosome products right now, like topical ones? It's really variable, you know, so it's hard to decipher risk when the products can have other actives or other formulations within them that could either be driving benefits or driving adverse effects. So exosomes in and of itself could either be active or not active. And certain types of exosomes, maybe if it's from sourced incorrectly, can be more inflammatory.

16:51So you just need to be very diligent on that sourcing. There's also considerable variability from sources. So if you have even the same source, let's say you are looking at adipose mesenchymal stem cells, that's coming from one donor usually. So if you have a 35-year-old male who has donated their adipose to make a mesenchymal stem cell exosome line, it's kind of like this sourdough starter analogy where you have it like this base and then you're making X amount of sourdough bread or X amount of mesenchymal stem cell exosome from that one specific donor. but after you run out, then you have to go find another donor.

17:31And then now maybe you're at a 45 year old female going through perimenopause and there are changes that are coming through that source that was different from the previous source. So you're going to see batch to batch variability in some of these exosome products that we have right now. So that's important to keep in mind. That makes sense. That makes a lot of sense. And it's very insightful to know that, And I want to actually shift, I think you had brought this up a little earlier, where things like growth factors, for example, growth factors in peptides, I know they also get classified in that regenerative skincare category, and people are making products with growth factors in them or growth factor memetic sequences.

18:14So what do we need to know about growth factors? Do they actually go and help with signaling between cells when used topically? I mean, what are your thoughts around them? Yeah, growth factors certainly do have a lot of benefit. Physiologically, we see during wound healing, certain growth factors are upregulated. And then with even scar formation or other types of healing, other growth factors are downregulated or upregulated. So certainly physiologically, growth factors make sense. But they do in the context of human healing where it's controlled release. Where I get concerned with exogenously applied growth factors is it's a pretty powerful signal, first of all, so continuous application of a growth factor signal.

18:57Topically, you could be over-activating proliferation pathways. So there is concern of people when they talk about pre-cancers and skin cancer over-activation. If you are over-activating certain pathways through certain types of growth factors, that is going to be a consideration. But second and probably more important is the actual delivery of the growth factor. So are some of the growth factors way too large and they just kind of sit on top of your skin and the stability of the growth factors, do you need to microneedle the skin to allow the growth factor to be better delivered as we know and do in PRP, for instance.

19:36So with acne scarring, for a lot of our patients, we are microneedling and then we apply topical PRP, which contains a rich cocktail of growth factors that's endogenously produced. So I just worry with exogenous growth factors about the timing of it, the duration of it, and the stability of it. Makes sense. Yeah, that's really fascinating. And I always wonder because also there's not a lot of transparency, I feel like, in the growth factor products. They don't really tell you what growth factors. They might be like, oh, this is a growth factor mix. And I'm like, I don't know what that means. It's a little scary.

20:11But on the same topic, just to dive in deeper, when I think of regenerative medicine also, like it also bleeds into, I think, what we're now calling longevity, which is like, you know, maintenance, right, of our skin health. I'd love to get your perspective on this. I know that you, before the call, had mentioned vitamin D, and I think vitamin D is an amazing topic. And I'd love to have you kind of tell us about that and just what skin longevity means, right, in this context of like, overall, everything that we're doing and what we should be thinking about? Absolutely. So let's break down regenerative medicine from longevity science.

20:48And I think that's the first line of distinction. A lot of people talk about it in parallel, but it's really important to know that they're synergistic, but they're different, right? So when you think about regenerative medicine, this is what we started off talking about. This is more of ways that a body heals. It's a repair, regenerate, renew. Think about regenerative medicine as a build process versus longevity science is a prevent process. So longevity science is a defense driven mechanisms. And I always say the number one skin longevity product that we have is sunscreen. So it's, it's a protective factor that if applied regularly, broad spectrum, you know, reapplied, you're going to see an amazing result in your skin because it confers resilience.

21:40So longevity is this idea of building skin resilience because you're adding protection versus regenerative medicine gives you reparative tools and building tools. It's not necessarily one in the same, but there is an overlap. I think that if you're kind of thinking through the circadian biology of the skin, where the skin naturally during the daytime can help protect and prevent damage. And it's kind of going through that defense mode in the daytime. And then at nighttime, the skin circadian switch to offense or rebuild repair protection. And it kind of switches to that build mode. So that's where you can kind of think about regenerative actives being more stronger at night versus longevity products and sunscreen being stronger during the daytime.

22:30So that's one way to kind of distinguish where these two can play within our skincare regimen, but also where their synergy and maybe applying together makes sense too. It makes sense. Yeah. And talking about vitamin D, I mean, you brought up sunscreen. I know a lot of people worry about, well, if I use sunscreen too much, I'm not going to have enough vitamin D. And I'd love for you to kind of debunk that myth or tell us a little bit more about that, because I see that a lot. People are concerned about that. Absolutely. So the short answer is you can still absorb vitamin D or UVB enough to support vitamin D production at the level of the skin with just 15 minutes of sun exposure with sunscreen on.

23:14And I think the reason why people are afraid of sunscreen is because they think it completely blocks out any UV absorption. But you may have noticed that people, even if you wear sunscreen, and if you're going outside, and if you're diligently reapplying, some people still get a little tan. And that's partly because you're continuously absorbing UVB. Unless you're truly protected and not exposing yourself at all with sun protective clothing, the UVB still penetrates through the skin with sunscreen on at a lower extent. And this is because of a lot of different things. First, maybe not enough application.

23:54Typically we need to apply probably three to five times more sunscreen than we think we do. And then improper reapplication. So we don't reapply as often as we need to, or as much as we should. And then the SPF factor could be slightly variable or maybe not broad spectrum enough. But even if you're doing all these things and going outside with that SPF 30 or higher on 15 minutes, you can still absorb the vitamin D that you need. In fact, the body has ways to make vitamin D byproducts if it produces too much. So we actually have mechanisms of combating vitamin D toxicity types of levels. So the minute that your body makes, you know, we basically take UVB light that comes through, and then there's this pre-molecule 7-DH cholesterol.

24:47So it's dehydroxycholesterol. And then that gets converted to pre-vitamin D, and that goes into vitamin D3, which is an active form. So the skin doesn't just make that vitamin D3 active form. It also activates it. It senses it. It uses vitamin D receptors to activate it locally. But if it makes too much or if it has too much, it starts making vitamin D reservoirs. So we have lumisterol as an example of a vitamin D reservoir. That's basically a by-product that just gets made because your skin has enough vitamin D and it just is almost like a standby product where we don't really have full understanding of its use.

25:28It just kind of becomes extra, if you will. So I would be less worried that we're worried about skin cancer risk and things like that and making sure that you are properly applying sunscreen and going outside for just 15 minutes a day or 15 minutes of light exposure to UV light to be able to get that production needed for vitamin D. That's really fascinating. And one thing that comes to my mind is we've seen in the last few decades, I think, an increase in people who have a deficiency in vitamin D. I know a lot of internal medicine docs, they always talk about this is that we are seeing a spike and people just not having enough.

26:06And so, I mean, in your opinion, what do you think is really contributing to that? Because I think that's really playing into this narrative, right? Of people pretending like it's because of sunscreen, but I mean, what are your opinion on that? There's a couple of reasons. Exactly. There's a couple of reasons for this. And I think partly we have to separate out the vitamin D that is locally made in the skin and then the vitamin D that you do have to take by supplementation and oral dietary needs. So that is still a very important thing to be doing because you can make vitamin D further downstream and get activated in the liver and the kidney.

26:42So there are pathways that we need to be supporting for systemic vitamin D and the blood levels of vitamin D that you're seeing does not correlate to the skin levels of vitamin D. And unfortunately we don't yet have a good way of measuring vitamin D on the level of the skin, but we can just make inferences from blood. So if you have low levels of vitamin D, it's true. You're probably not getting enough vitamin D exposure and it could either be, you know, going outside and getting sun. And even that 15 minutes a day, we're, we're becoming creatures of, of habit that tends to stay indoors a lot.

27:21So a lot of us, you know, unless you're driving a lot or going out in your car, we're no longer outside as much as we should be. So I think, I think part of it is just the movement of the indoor habits and just being indoors a lot more. And then the second it is, if you're darker skin types, you do need to have longer exposure, maybe instead of 15 minutes, it's 30 minutes to be able to get that absorption of vitamin D because of the melanin content of your skin. So there's a couple of reasons from a skin topical exposure, but the other aspect of this is oral intake too. You do need to be supplementing vitamin D through foods and diet and even oral supplements to be reaching some of these levels.