In the first episode of the podcast, Dr. Fan and guest Dr. Michael Longaker, a pediatric craniofacial surgeon and stem cell researcher, delve into the transformative role of stem cells in plastic surgery and aesthetics. The discussion begins with Dr. Longaker's unexpected journey from athlete to researcher, highlighting his significant discovery of scarless fetal wound healing. He outlines his research on skeletal stem cells and their potential applications for arthritis treatment, while also addressing the challenges of bringing these findings to clinical practice. The episode covers the basic types of stem cells, current clinical applications, and the importance of regulatory oversight amidst the rise of unproven treatments in aesthetics. As the conversation progresses, Dr. Longaker shares insights into future possibilities for scar-free healing and better fat transfer techniques, while underscoring the essential role of interdisciplinary collaboration and lifestyle factors in advancing stem cell therapies. Key future action items include submitting a pre-IND application to the FDA and beginning large animal studies for cartilage regeneration.
Table of Contents
🔬 Introduction to Stem Cells (00:00 - 08:41)
- Podcast focuses on stem cells in plastic surgery and aesthetics
- Guest: Dr. Michael Longaker, pediatric craniofacial surgeon and stem cell researcher
- Dr. Longaker's background: From athlete to accidental researcher
- Discovered scarless fetal wound healing during research fellowship
🧬 Stem Cell Research Journey (08:41 - 17:58)
- Dr. Longaker's transition from reluctant researcher to passionate scientist
- Key discovery: Skeletal stem cell identification in mice and humans
- Potential application: Regenerating cartilage for arthritis treatment
- Challenges in translating discoveries to clinical applications
🔬 Stem Cell Basics and Applications (17:58 - 28:34)
- Definition of stem cells: Self-renewing cells that can differentiate
- Types of stem cells: Totipotent, pluripotent, and lineage-specific
- Current stem cell treatments: Bone marrow transplants
- Caution against unproven stem cell therapies in aesthetics
🏥 Stem Cells in Plastic Surgery (28:35 - 38:18)
- Dental stem cells: Potential for banking wisdom tooth stem cells
- Challenges: Ensuring stem cell survival and predictable results in fat transfers
- Future possibilities: Scar-free healing and controlled tissue regeneration
- Importance of FDA approval and clinical trials
🧪 Research Progress and Challenges (38:18 - 47:49)
- Breakthrough: Potential scar-free healing treatment entering human trials
- Advancements in gene editing (CRISPR) for genetic diseases
- Importance of interdisciplinary collaboration in scientific discoveries
- Balancing immune system response for better healing and transplant acceptance
🔮 Future of Stem Cells in Aesthetics (47:49 - 57:36)
- Potential for predictable fat transfers and tissue survival
- Goal: Ability to contour without foreign bodies
- Challenges in addressing overall aging process
- Current limitations of stem cell treatments in aesthetics
- Importance of lifestyle factors in aging prevention
[00:00:00 --> 00:01:26](Fan)
Welcome to The Fan Method, the aesthetics, health, and wellness podcast dedicated to helping you look and feel your best, inside and out. Stay tuned as we explore what stem cells are, the latest innovations on how they're being used in plastic surgery and aesthetics, and the practical considerations you need to know if you're thinking about incorporating stem cell treatments into your own personal health and rejuvenation. Whether you're curious about the science or considering a procedure yourself, this episode promises to arm you with the knowledge you need to know to make informed decisions and to separate the hype from the reality. Before we dive in, I want to remind our listeners that today's discussion is for informational purposes only and should not be considered medical advice. As with any medical treatment, it's crucial to consult with a qualified healthcare provider to determine if stem cell therapy is right for you. So let's jump in and discover the truth about stem cells. I'm your host, Dr. Larry Fan. Our guest today is Dr. Michael Langecker. Dr. Langecker is a pediatric craniofacial surgeon. He's a professor at the University of Michigan at the University of Michigan. He's also a professor at the University of Michigan at the University of Michigan. He's a professor at the University of Michigan at the University of Michigan. He's a research scientist and co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. He has dedicated years of research to tissue repair, tissue replacement, and tissue regeneration harnessing stem cells, leading to more than 1,200 peer-reviewed publications. Dr. Langacker is truly a global leader and role model for those physicians and scientists who aspire to improve patient care through regenerative medicine. Dr. Langecker, thank you so much for joining us today.
[00:01:26 --> 00:01:28][Longaker]
Thank you for having me, Dr. Fan.
[00:01:28 --> 00:01:35][Fan]
I'd love to learn a little bit more about your background and how you came to be one of the leading researchers in stem cells and regenerative medicine.
[00:01:36 --> 00:24:14][Longaker]
Well, that's an interesting question. I am an accidental everything. So I was born and raised in Detroit area, Detroit, Michigan, on 13 Mile Road, if that's meaningful, 8 Mile, the movie of Edmund N. So I'm in the town of Warren, which begins at 8 Mile. 0 to 8 is Detroit, then Warren, 8 to 14. I'm on 13 Mile. My father was a professional baseball player. My mother was a housewife, lived in a 900 square foot home, 10 feet from our neighbors. It was a fantastic place to grow. It's the only thing I knew. And I think two things really that I was blessed with as I look back, I could always run and jump. So I was a heavily recruited athlete in football, basketball track, and I had a good memory. And somehow, I've leveraged those two things into my career. And my dad decided in those days, there's no ESPN. So he decided I should go to Michigan State for basketball, which I thought, okay. So we go to Michigan State, could never have predicted Magic Johnson would come. We'd win a national championship and the most watched game of all time. Not even remotely would expect that. And I wasn't a star. I was a star in high school, but there's a pecking order in the world and he's going to be one of the top five players of all time. So it was a fantastic experience. And I think that's what I'm most proud of. I went to Harvard for medical school after that, thinking I was a computer error. Well, no computer, whatever. I was a clerical error. But I get into Harvard Medical School. I didn't do any research. In fact, I played basketball in the summers with Irvin and my teammates while my classmates were doing research. So I always heard about UCSF. I wanted to match there in general surgery. So I matched there in general surgery. Halfway through my five years, we get a new chair surgery. And then I got a new chair surgery. And then I got a new chair surgery. This is a true story. He's looking through my file, half glasses, posh British accent from Eritrea, Haile Debas. And he says, wow, you're a really good student, but you've never done any research. And I blurt out, Dr. Pham, without even thinking, you know, Dr. Debas, I don't want to do any research. So he just looks at me and he says, a frontal release is something that's usually before age two. A two-year-old will think it and say it. Or like after 90 at Thanksgiving dinner with grandparents. And he says, I don't want to do any research. I don't want to do any research. He said, you are old. I said, 29. He said, well, wow. Okay. So that's amazing. He said, now I'm going to ask you to name your name tag. So I did. Resident three in surgery six. Did you read mine? I thought, oh boy. He said, so we're level set here? I said, yes. He said, so this is an important question now, Michael. How would you like to do a year in the lab? I said, I'd love to. If he writes down trainable question mark. So I'm like, oh my gosh, what did I just do? So in those days, you start in July 1st, as you know. So sometime in early June, I get a note, a typed letter from the admins saying, you're going to be starting in the pediatric surgery lab with Michael Harrison. I said, great. Now, your audience wouldn't know this, but in 1981, Dr. Harrison was the first person to operate on the unborn patient, to open up the abdomen, open up the uterus, operate on the fetus, because it'd be too late to wait. Heroic, heroic surgery. So I'm joining the lab in 87. So he had probably done seven or eight cases. Anyway, I screw around for three months, moonlighting. He asked me at a group meeting how moonlighting is going. And rather than saying, you know, I don't know, I said, I love it. I'm making a lot of money. And he's like, oh my gosh. Okay. So he said, well, why don't you look at the way you heal before you're born? So guess what I blurt out? I don't think that's a big medical problem, since you're the only one in the world making, you know, wounds on embryos. So he ended up, I did, I was operating on a fetal lamb the next week. And lambs are born at about 150 days, long gestation. So I operate on a 70-day lamb. And I make these two big wounds, excisional wounds, close the uterus, come back three weeks later, and open it up, perfectly normal. So my first thought is, they were twins. My first thought is, oh my gosh, I've opened up a twin I didn't operate on. And the other fellow said, no, this was, you know, I'm going to do it. So I'm excited. I take pictures. We get that there's no, we have to develop code of crumbs at ArcherFam. This is 1987. So I put it in the projector, super excited. My wife's excited. And he says, what? I said, there's no, you're right. There's no scar. He said, but how do I know there was a wound there? I was so mad. I was like, oh my gosh. So I had to do another operation the next day. And I put marking sutures around, but I went from euphoria to these people don't believe me so anyway that's a long-winded explanation to say i was forced in the lab i was assigned a project by the one person in the world who could think it and for 37 years i'm still working on that so i then thought he said you should be a pediatric plastic surgeon it's called craniofacial surgery i had no idea what that was because it's not like in general surgery you see stuff we did a lot of time on plastic surgery no time yeah so i ended up doing nine years of general surgery instead of five so my one year in the lab became four changed my whole life i was obsessed with scarring and why eight billion of us outside the uterus heal with a scar and the millions of tens of millions of embryos inside the mother's womb heal without a scar yeah and when does that change it's latent gestation so that was my career i then went on to do plastic surgery for two years and then a year of craniofacial surgery and went back to nyu where i was and had a lab um and it was an interesting time because i had to build labs from scratch there was no it wasn't like ucsf which i was blessed with these incredible labs and surgery so it all worked out and i moved out to stanford in stanford ucsf merger 24 years ago and i would say that the discoveries that i'm known for are were either someone asked me to do something like dr harrison who's a doctor who's been doing this for a long time and i'm still my mentor or training with very talented people at stanford in medical school residents etc who made discoveries so i think i've been blessed to be at great teams just as magic johnson was a fantastic player and i was okay yeah um that was a little humbling because in high school i wasn't okay right if you go from big fish to minnow um but it all worked out um so i think i'm a kid from the detroit area who somehow become a scientist i'll leave it at that wow that's that's fascinating that's such an amazing journey and um you know when i hear it it sounds a little bit of like the way life works there's they're they're often going to be a lot of serendipity involved and at the same time there's some threads i can already sort of hear through your life you know i'm curious i wanted to ask you how did you go from someone who had never done any research and even you know it sounds like didn't particularly have a lot of interest when the topic is brought up going from that to being an extremely passionate dedicated capable sort of researcher and you know i can share with all of our audience um as someone who also trained at ucsf um well behind behind you but you know i remember sitting in the lab when i was doing research and reading some of the the studies sorry you had to do that no to me it was actually fascinating and it really showed the potential of sort of regenerative medicine um but how did you go from sort of hey research was kind of a concept to to you know what oh my gosh this is something i'm so dedicated to well it wasn't planned so um i'm forced in the lab in fact dr harrison uh i had finished on the congenital heart surgery service and i was asleep in front of his office on july 1st because i'd finished at 5 30 a.m so he told me to go home take a shower and take a week off and for me there's a panic attack i'd never had like a week off to do nothing so i get my yellow pad my briefcase i don't know i'm ready to go the next day but uh so i didn't know what to do so it was a panic attack until he gave me an assignment so i'm not a fumbler but remember it's not my idea now he does not like that because i've received a lot of major awards when i've asked him to attend and he thinks it trivializes my role but i said it's true i didn't fumble it so so it happened on the margin every day there but the reality was everything every abstract i wrote people was it was accepted every manuscript it was just like people were starved for what are you talking about healing without a scar so i would say i go from an r3 at where you're doing cases and feel like you're doing things but you're not at the level of a senior professor to having an international reputation by the time i'm a second year in the lab yeah so i decided to do a second in my fourth year i now have a very large team the equivalent like the chief resident there we had written two nih grants we had published you know over several hundred papers which is absurd um and i was really it was fantastic because i felt like okay i'm really leading this field and when i go back to trauma and i'm doing my first whatever gunshot wound to the liver i won't be leading i mean you know it's it'll be a difference so it was a different it was a very uh i guess a dramatic positive reinforcement with every presentation um and i was being asked to do all these things around the world not as a professor i would have to say you know i think you want dr harris and no no we want you and i'd be like okay i'm a postdoc so everyone was always disappointed when i got off the plane because of you know it wasn't some senior professor but so i thought okay we're just going to keep going and then the same person that forced me in the lab said okay now you did three years of clinical it's your fourth year in the lab i think you're overdoing it i'm like okay what so he said finish now and i'll uh get your phd we'll bring on the faculty or if you finish surgery then you'll have more options so i thought okay i'll finish general surgery so it was like a little bit every day larry and but it just at some point i realized okay this is uh incredibly fascinating because we're writing this trajectory um and i went from reluctant to still not totally comfortable but you know we're doing papers i wrote textbooks it was absolutely insane and i can't think of any other place that would provide that fertile of a soil to take someone with no background who is a hard worker and i hope i can give my research fellows handoffs like that because dr harrison's still alive he's an amazing person and now there are five or six hundred fetal treatment centers around the world so you imagine that impact yeah and i'm one of four or five hundred people he trained yeah so for me i'm very grateful to ucsf to give you that opportunity i could never have predicted it in my whole life and then it just over time things you get better at it so you know i'm i'm asked the question um how did you discover the skeletal stem cell so for your audience they may not know that you have a single cell that gives right to hard bone cell and you have a single cell that gives bone spongy bone and cartilage and it's called the skeletal stem cell so that was a post a grad student who began a postdoc and i still remember the day i saw it it was in a confetti mouse rainbow colors and there it was and i thought oh my gosh you know there's a moment that you look back yeah so that was a big deal and then three years later we just identified it in humans so now i sit here and i think for the audience listening to this they're thinking okay so this guy went from basketball to basketball and he's like oh my gosh he's like oh my gosh he's like oh my gosh basketball to this to that to that so to say where's the puck going if you're a patient so there are 78 million americans today who have arthritis and that's going up in an aging population so we do anti-inflammatory drugs if you have it's really advanced you have the incredible ability to have a hip replacement and your pain is gone right away i don't know what people did 80 years ago dr fan but they probably drank or whatever wheelchairs but now we're having an ability to do that question is you know we also do four million times a year you're looking in a joint we don't look in the heart with the telescope or the liver but orthopedic surgeons have arthroscopy you know it it's millions of times so then i thought okay what can we do with this so i thought well in mice where all experiments start let's develop arthritis by doing a tear by taking away the ligaments think of the acl going out yeah they walk funny they're in the arthritis and then i said what could we do a microfracture surgery so microfracture surgery is you have a hole in your cartilage it's sore it's painful the orthopedic surgeon drills hole through it so that the bone marrow cells come up and that's done probably a 500 000 times a year but it's a fibro cartilage a scar cartilage it doesn't last so i said well if we do the if we use these two things which are fda approved could we generate cartilage and that would be a big deal so we're able to do that and that post published two years ago and now we're just starting large animal models um so i there's an example where fundamental discovery is coming along for it's not fast enough because you want it yesterday but if you're a surgeon scientist you want to make something you want to make a discovery that helps patients in your office or anyone's office so i think discovering something is great but if you're a surgeon scientist you want to make something you want to make a discovery great because there's no translating without discovery so there's an example the skeletal stem cell if it works in pigs could we do this to get uh lesions that are not large enough to have a joint replacement to regenerate i think we can we still have work to do but um that's an example of what a patient on your this podcast could think of similarly you have thousands of people listening on your podcast and you start with the concept of you can get a wound to heal without a scar in utero so we talked about getting a wound to heal without a scar a plastic surgeon would love that because instead of remote incisions to hide it you can work wherever you want so the question is how's that going to work out so we made the discovery that you could heal without a true regeneration now think about it scars are a little different than normal skin yeah on the skin you can't heal without a scar they don't have hair they're bare they don't have sebaceous glands they don't look like the skin around it and they're only 80 percent as strong as skin despite all that collagen most people think the scar is stronger so you have to show all those things were met so now we did it in red direct pigs your patients on this podcast or the listeners don't realize the most human-like skin after the two of all animals are pigs humans your patients have special situations we can't under heal with ulcers we overheal with hypertrophic scars and keloids so humans are very unique so the the pig skin is the most like it so now on you know somewhat confidentially we just submitted the paper it works in large animal models so on monday we sent in the first pre-ind called interact with the fda to say we would like a human clinical trial using the drug that got mice to heal without a scar and that's like a huge deal yeah 1987 to now is 37 years so for your audience i guess i'm a slow learner but but i'm persistent so here we are standing at the threshold so being a pediatric plastic surgeon you know because you've done these operations if a child is born with a cleft lip or palate it's a significant thing in their life and its form and function so between age of 12 and 18 we're going to have 15 people it's routine to get a scar revision three different doses at pacific or children's hospital if we get approval to go forward yeah so for the audience you say how do you do that well we were really lucky and i think it's really wonderful to be lucky because the drug that prevented scarring in mice is called is a blocker of the last gene the transcription factor that gets activated when a fibroblast uh senses strain the cell that's going to make the collagen yeah this drug was fd approved 24 years ago for macular degeneration so you inject it in the eye iv and then it has a special ingredient that activates it in the in the in the light in the eye to block blood vessels that has nothing to do with what we're doing yeah but it means tens of thousands of americans have had an iv yeah and we're talking about a one-time local injection like you do marcaine on the way out yeah so that is exciting for me the fda may ask for a few other things but for 24 years americans have been using this iv and that dose is 50 times the local injection so i always ask do surgeons do injections on the way out yes patients don't realize we inject lots of things like long acting anesthetic whatever it take doesn't add any time in the operation and the toxicity of this drug is very well known yeah because it's been given by me so you know call me crazy but i hope that we'll have we'll get approval to start a first stint human now a lot of patients listening to this don't realize how different it is if we have a combination of oni drugs drugs and avian drugs but you know can be approved right so this is an orphan indication there's less than 200 000 people people a year who are afflicted with cleft lip and palate. It's actually 7,000. But orphan means under 200,000. So for example, Botox. Patients listening to this may be getting Botox, paralyzing their muscles. That was approved for facial tics after Bell's palsy, where you just, you know, for the patients listening, you may not know, but involuntary muscle spasms after being temporarily paralyzed. So the off-label use over time has gone not to that. So I'm not naive. I realize there are 50 to 80 million incisions a year. Only 7,000 are in clefts. I want to start with that because that's important to me. But I want to get it approved in an orphan indication. It only requires two trials, not three. But it's a smaller market, but it's important to me. But do I believe in my heart five years from now that patients will be able to get their incisions to heal a lot of scars? Yes, I do. And that's wonderful if you're a patient out there. Because I'm always asked, you know, Dr. Phan, are scars important? And I say, only if you have one. And only if you have one on your face and you're four years old. If we don't get that child looking as normal as we can before kindergarten, guess what? Frontal release. Someone asks, what's wrong with your face, right? So, you know, you make these fundamental discoveries and your patients and audience are wondering, okay, when's it going to hit? So, I can say, if we do the first in man in 2025, I'm hoping that by 2028, we would have the ability to use this in surgery. Now, lots of reasons it won't work. But I think the preclinical data on mice and pigs would suggest it will. And we know that tension is not your friend. You know that instinctively. So, yes, there's a lot of work to do. But I'm just thinking, it's been 37 years I'm either going to do this or die trying. Because it's, you know, you work on something for so long, and I get probably a thousand emails a month. You know, there are people who buy Vizudine, ask the surgeon, it's not how, we'll get into that. So, what happens? Our patients are desperate to use something. But we haven't done the trial yet. So, yes, you can buy this drug for the eye, you know, for eye, but you can, it gets activated by light. So, it's not so, there can be some standing, there's lots of reasons. And I'll simply say to the audience, I'm more anxious than they are to have this done. Because it's been my life since 1987. And I get it. There are people who are listening to this podcast who say, you know, stem cells, I mean, we're 50 years into a war on cancer with Richard Nixon, or 60 years. Stem cells were having around embryonic since 2000, in 1998. Why hasn't it impacted? It takes a long time. But I'm here to say, at least in the areas of arthritis, with 78 million Americans, 80 million incisions, there are spectacular things coming that are not pie in the sky. I would not want to be the FDA commissioner. Because at the end of the line, at the end of the day, you're signing, and you've done 1000 patients or 2000. But what if the complications need 1 million patients? What if the complications need 1 million patients? Right? How many? I think about it every day. Insulin is the most safe drug in the world. Right? How many millions of Americans are on lipid lowering drugs? Well, what if it takes 100 million lives before we see a complication? So you never really know. But you have to say, have we done everything to be safe? So it prolongs it. But at the end of the day, the United States FDA, you must be safe and efficacious. And in Europe, also, a very first world situation, only safe. So the bar here is the highest. I'm frustrated by it. Your patients are frustrated by it. But it's the safest way to do it.
[00:24:14 --> 00:24:46][Fan]
Yeah, absolutely helps keep us safe. And that's, gosh, that is such an incredibly exciting sort of development. And, you know, I wish sort of you and the team much luck with getting that approval.
{Longaker}
Yeah, I certainly hope if the FDA is watching and listening that, you know, that they say yes, obviously, they're locked up. But I'm sure they're going to be safe. And I'm sure they're different sort of, you know, things that they need to assess to make sure that they feel, hey, this is something safe to do. But given that the medicine has been used, you know, already approved for different uses, you know, it strikes me that hopefully it's just something that From your lips to God's, to the FDA's ears. Yes, exactly. And, you know, I think it's important that the people listening understand why things take so long. So I probably get an email every day, at least, from someone who says, can I have liposuction? Can I isolate some stem cell from there? And can I have it injected in my heart or joints? And I always say, well, you can do all those things. It's very legal to have liposuction. It's very legal to do arthroscopy. But we don't know if that's safe and effective. So, but I'm going to another country. I'm going to Thailand, Brazil. I don't... Name a country there. And I always think, okay, those people, I believe those clinics are taking advantage of people who want to look younger, want a longer life for their mom or dad. But there's a reason why we do randomized controlled trials. And that's not what patients want to hear. It's not what I want to hear, but it's not perfect, but it's the only way we can do things safely.
[00:25:58 --> 00:26:11][Fan]
So stem cells are often sort of, you know, oftentimes... Talked about as the future of medicine, and yet it's a concept that's mysterious to a lot of people. Can you give us a brief overview of what stem cells are and why they matter?
[00:26:12 --> 00:28:03][Longaker]
So this field has emerged very rapidly. So let's think the egg and the sperm come together. You have one cell. From that one cell, you have over 200 types of cells in every tissue developed. So it's a cell that can self-renew. It can give rise to a daughter cell that's just like that one. As well as another cell that's becoming something else. So if you just think one cell to the whole body, that's a spectacular example of what they're capable of. And then each of the tissues in the heart or in the skin or in the liver, there are resident specific stem cells. So if I say, I back out of a driveway in your house, I'm going to drive to Chicago, there's a lot of ways I can get there. But when I pull into the driveway in Chicago, I'm committed. So you go... So from becoming any type of cell, that would be totipotent. And then there are cells that have become bowel, as an example. And those are skeletal stem cells, but they're not going to become nerve. They're not going to become eye. They're not going to become hair, as an example. So it's a cell that can self-renew, make more of itself, and become something else. Now, how many of the something else are totipotent, egg and sperm, pluripotent, nearly everything, and then linoleic? Oh, you have stem cells in your liver for all the cells in the liver, but they're not going to become bone. So they're capable of a lot from everything to less than everything. But they're why we renew, for example, right? You have many more cells than you're born with throughout your life. So there's a role for them in normal homeostasis. Normal life requires self-renewal in rejuvenation of tissue. So that's an example. And then there's a cell that can self-renew, and that's an example of what they are.
[00:28:04 --> 00:28:09][Fan]
Yeah. Yeah. And what makes stem cells so unique and so important to clinical medicine?
[00:28:11 --> 00:29:30][Longaker]
Well, they offer unlimited hope and a blueprint. So if we understand, pick an organ. Give me an example of an organ. Skin. So it's the largest organ in the body, or it's the most available organ in the body, unlike the liver, for example. No more important or less important, but it's so readily available. So skin develops in a certain way. When it's developing. The ability to use stem cells to recreate that offers our ability to reform that or regenerate that in such a way that you would want that. Most of the people listening don't realize that a lot of the dust in your home, if you don't have a pet, is your skin. So every 21 days, this is a spectacular example. Every 21 days, you have an area of stem cells that migrate up and become... Let's call it less and less viable until they're the outer layer of the skin, which is actually more of a dead layer that sloughs off every three weeks. So it's not like we're molting like a snake, but there's an example. Patients don't even realize their skin is being replenished all the time. That's an example of how stem cells are used. And it's different for different organs. Some, like the brain, don't do that. But the skin is an example where it does do that.
[00:29:31 --> 00:29:44][Fan]
Absolutely. That's great. So now that we understand sort of the foundations of what stem cells are, can you tell us about applications of using stem cells today in plastic surgery and aesthetics?
[00:29:45 --> 00:36:56]][Longaker]
So the way they're used today is not how they're going to be used in the future. So I would envision a future five years from now, 10 years from now, where your patients have an incision made wherever it's easiest for you. I mean, I always ask patients, why do you think we put a breast implant through the armpit? Or why are we doing surgery through keyholes? It's not easier, but you don't have the scar, right? So be able to make an incision anywhere you want. You'd be able to do anything you wanted and have total regeneration. So instead of injecting things in that give some contour, you could say, look, I'm going to inject some skeletal stem cells, but I only want them to become cartilage in the nose, and you're not going to have to worry about it. It's going to be shaped just, it's yours. They're your stem cells. So the ability to induce tissue wherever you want it and whenever you want it in a controlled fashion. So one of the things that people worry about, if you got embryonic stem cells, now this is a little different, so it's not yours, okay? So if I had an embryonic stem cell that maybe doesn't have self-nonadjustment, self-identity, and your audience should know your cells are your cells. There's nothing more personal than your cells. Your cells in my body, I'm going to reject that and conversely the same for you. But let's say you have embryonic cells and I put those under the skin because I want to have a more prominent cheekbones. I'm making that up. Those cells are so unorganized. Some of them could become hair. Some of them become liver. It's called the teratoma. It's all these tissues. We can't have that. So we have to have cells that are fully differentiated to what we want. And that takes a long time to understand that because one multipotent cell would give you the potential for having bone in an area you don't want it or a tooth to form where you don't want it, et cetera. So you have to have all the correct guidance on those cells, which takes a long time. Remember the controversy 20 years ago. Your audience may remember this. Like, are we going to sell? Fertilized embryos. What are we doing that for? And that was outrageously controversial in 1998 to about 2008. What are we doing? How are we doing it? Is that possible? But an orthopedic surgeon from Japan won the Nobel Prize, Shinya Yamanaka. And Shinya said, your audience sitting at home, they could put a Q-tip in their mouth and swirl it around, end up with 500 cells from their oral mucosa. And they're wondering, but I don't want to sell. I want to sell. I want to sell. I want oral mucosa. I want to regenerate something. Think of something else. Okay. Dr. Yamanaka said, I'm going to test a number of factors, brute force, and was able to think of four factors, four transcription factors, master genes applied to those mucosal cells that made them like embryonic, but they were already yours. So you don't have to be within 500 miles of an embryo. That's why we don't hear about the controversy anymore. We can take somatic cells, your cells. And reprogram them. So you back them up, but now you have to show they can only become what you want and not something else. So that's still in the body. That's still making sure they're a pure population of only cartilage cells or only skin cells or only hair cells, right? And we're not quite there yet because we can't have liver forming where we want skin. And we can, we just,most people wouldn't want it. Now, there's probably a lot of listeners who have heard about stem cell treatment. You know, today, and particularly in the aesthetic world, there are, you know, there are terms floating around like stem cell facelifts and stem cell, you know, fat transplantations and so on and so forth. You know, what do you think is the real sort of current status of those types of treatments today? Are they, you know, are they safe? Are they proven? Are they effective? Are they things that you would recommend, you know, in today's world? Or do you think it's all, you know, hype more than anything else? So I want to make sure, your listeners know that I'm a board-certified plastic surgeon trapped in a stem cell biologist body. So I'm not here to be critical of any colleague or any surgeon in the world. My role is to make sure that things are done with randomized controlled trials. So if I said platelet-rich plasma, how many times is that injected in the joints or whatever, right? So I always start with that as an example. I don't know if it works, but platelets aren't even cells. They don't have nuclei. So there's, when you start with that, you realize where I'm going. They may work, but they may not work by integrating into, I have 10 a cell, but whatever, whatever the patient has, I have carpal tunnel, whatever it is. Okay. That's fine, except they may not last long. And that's perfectly fine, Dr. Phan, as long as they deliver a payload that modifies some behavior. What patients think is I have to have a cell incorporate and rejuvenate. Not really, as long as it's modifying inflammation. And I don't know whether that's true. Is it on lots of billboards? Yes. So the medical tourism is particularly problematic in the aesthetic area because people want to believe, right? I mean, liposuction is wonderful. Almost a million people have it, but to say, okay, I'm going to suck out my fat. I'm going to isolate cells. The blood vessels around fat, not the fat cells themselves. And those have the ability to become several different tissues. And I can inject them into my knee. I'm making it always up. People are always complaining about joint pain. And I can do this. I can go to a course. You're board certified in plastic and reconstructive surgery, but you could take a course in Florida on the weekend to learn lipoaspiration, I assume. And you can learn how to use ultrasound to inject it in the knee. That doesn't mean you should be doing it. Because cartilage, as you know, and your patients may not know, has no blood supply. So if you tear your cartilage, you take it out. So I just caution everyone, if it's a randomized controlled trial done by a board certified expert and stands behind it, that's fine, right? But a facelift is a complicated operation that experts like you perform daily. It's real surgery, right? These are real operations. Things can work out very well, which is expected. But sometimes patients have a problem under anesthesia. It has nothing to do with the procedure. So facelifts are a real operation and done to tighten skin and soft tissue. Do I really think you could put a cream on and get the result you get with a facelift? No. I'm sorry, I don't. We're not there yet. Could we be there someday? Yes. But right now, we're not there for a lot of the indications aesthetically.
[00:36:56 --> 00:37:07][Fan]
So I know you're involved with some groundbreaking research using a different type of stem cell, dental stem cells, your collaboration, your work with companies like Stemodontics. Can you tell us a little bit about that work?
[00:37:07 --> 00:39:11][Longaker]
So that's an excellent example. The ideal source for stem cells would be from you, by you, for you, your own stem cells. You're not going to reject someone else's. So it turns out anytime you're discarding tissue as medical waste, that has a stem cell population, I'm always, stop, let's look at that. So it turns out about 10 million wisdom teeth, third molars, as you and I would call them, are removed every year and discarded. And the options are, do you want to take them home in a jar? Do you want to sit throw them away? Whatever. There's a third option now because the pulp, the soft tissue in the tooth, has stem cells. Now for your audience, you and I know what neural crest is. There's a when you're developing that gives rise to everything from the neck up called cranial neural crest. Those stem cells in teeth are highly likely to have those properties and they're yours and they're yours when you're young and healthy. So I love things like that because why throw them out? Because you don't know what's going to happen to your son or daughter, God willing, but you'll be ready. They're frozen and they can be coached into anything in this tissue, but these tissues are almost everything you need going forward. And frankly, we could probably coach them into become anything. So as the field moves forward, they're banked and ready. You're already asleep. You don't have to have a second procedure. So I see very little downside to banking your stem cells rather than throwing them out. And stemodontics is this very clever approach where you don't throw them out and they're yours forever. So that's an example. For example, know, just think of anything that's discarded in operation. Well, if it had stem cells in it, you'd be less likely to discard it, but very few things, 10 million of which are thrown out each year. So that's a really new example of how businesses are being created. So you bank your stem cells at a young age, which is great.
[00:39:11 --> 00:39:41]{Fan}
That's very exciting. And I know that reminds me of the old days, gosh, when I started practicing a long time ago, it was becoming a little popular to take some of the adipocytes of the liposuction to do the same thing. And it sounds like this is something that's even better that the sort of the source of the cells, you know, typically the age of the cells, as well as, you know, what kind of cells and what they can do, it sounds like it's even more powerful. Would that be correct to say?
[00:39:41 --> 00:41:46][Longaker]
Absolutely. And they're at a young, healthy age, less pollution, if you will, less things have happened to them. And it just makes sense to me. There's no reason to throw them away if you can keep them. And that's a new option. Of course, that wasn't available for me when I had my wisdom teeth out. But let's talk for a minute about what happens if you transplant cells into different parts of the body. So I think the audience should know that your immune system is for you, that we talk about personal medicine, right? Personalized medicine. So if I were to put an implant in a patient, something on their cheek or something on their brow or something in their, whatever, something in their lips, the body identifies that as foreign. And it has a foreign body response, breast implant. Let's talk about a breast implant. Usually major indications would be breast reconstruction after a mastectomy or breast augmentation. Those are two big categories. I think you'd agree. Those are not that patient's tissue. So the body has a reaction to that, a little, like a coating of scar over it called a capsule. So I think it's important that, and as we're aging, there are millions and millions of implants, some of which are aesthetic, some of which are not. I think if we could manage foreign body response, we could use a lot more of them. So that's one of the things my laboratory has recently worked on. That's a chronic form of scarring. Your body says, oh, not you, not me. I'm going to try to isolate this. That's a problem when it deforms the implant. It's also a problem if it's an EKG electrode or a pacemaker, right? So I think we're now on the threshold of being able to minimize foreign body response by coatings we've put on. And I think that's going to revolutionize how plastic surgeons use implants. If you can minimize the scar walling off as foreign, that would be great for your patients. And that's coming sooner rather than later.
[00:41:46 --> 00:42:37][FAN]
Obviously, that's tremendously exciting. So much of human medicine, health and disease, the two extremes, the balance... The balance of sort of too much or too little, right? Like foreign body response, hey, often too much of that creates problems at the same time. Too little of a response, and then sometimes there may be issues with healing or wound healing, for example. Not enough response, delayed healing or an absence of healing. Too much of response, we end up with a hypertrophic or overgrowth or hypertrophic or a keloid scar, too much scarring. Same thing with cancer and et cetera. How do you think... What do you see as far as how, as a scientist and as a surgeon, as a doctor, how are we going to be able to balance the two sides of the response of trying to get...
[00:42:37 --> 00:44:56][Longaker]
This is a great question, Dr. Fan. And I will use a spectacularly active system in your body, your immune system, right? Too much immune system that you can attack your own tissue, graft versus host, connective tissue diseases, many forms. Of musculoskeletal problems are examples of your immune system being overactive. It can be overactive because you had COVID or an infection, right? We need to fight infection. We need to protect ourselves, but too much of it is a two-edged sword. So as we learn how to modify our response to anything, especially foreign body, we'll be able to accept a lot more things. For example, the people not listening may not know as we're, as we sit here, we're not able to accept a lot more things. We're not able to accept a lot more things. We're getting closer and closer to having pig organs modified such that they would be tolerant in humans. Wouldn't that be great? I mean, everyone's like, what? They have these sugars on each cell that have prevented that, but now we're close. And that's going to revolutionize the way we look at transplantation. But too much and too little typify the immune system, right? You have an implant in, the body doesn't like it. It's should be obvious, but you're thinking it's ruining my reconstruction. It's ruining my aesthetic result because the immune system is trying to put a wall around it and deforming it. We'll be able to modify that going forward, but that's, you're right. Too much or too little defines wound healing, ulcers on a diabetic foot or a hypertrophic scar keloid. But I think we can modify the immune system such that it attacks the cancer, but doesn't attack the rest of the tissue. So you're right. We're, we're just beginning to understand what we need. You remember if you're on liver transplant surgery, UCSF is one of the leading places in the world. So steroid suppression, so they'll accept that liver is a nightmare for the wound. So, you know, we want to be smart about it and that's coming. So the immune system and connective tissue problems are very difficult to treat rheumatoid arthritis, other things like that. But I think we're getting better and better at how to modify the immune system specifically. So it's not a gross honor.
[00:44:56 --> 00:45:39][Fan]
And these obviously are, you know, significant issues that people have been working on for literally decades. And, you know, it sounds like you've indicated that, you know, for example, you've been working on, on sort of scarless wound repair for more than 30 years. And that sounds like you feel like we're very close in many of these key arenas. What do you think have been the principal, I guess, advances that, that have allowed, you know, that have gotten us much closer and, and maybe another way of asking this. As there are some people who may have been following the field for a long time, and they've also said, well, gosh, I've heard about this stuff for 20, 30 years. And it's still, you know, I still don't see it in real people. You know, why should I believe or be excited and feel like, hey, it really can happen in the next five days?
[00:45:39 --> 00:49:00][Longaker]
Look, I get it. The boy or girl who cried wolf, right? As I said, President Kennedy and President Nixon had a war on cancer. We still have cancer, right? Gene therapy was going to cure everything. Right. But you know what's happened now? We have remarkable breakthroughs with CRISPR, the molecular scissors, Nobel Prize from Berkeley, that were able to cure patients with complex disease, sickle cell, things like that, never thought to be possible, right? Those trials are positive. These people are having the defective gene cut out and replaced and be cured. I couldn't have sat here and said that five years ago. So I get it. Oh, don't talk about this breakthrough because I'm never going to see it. Well, here's an example where you see it. And, you know, having applied to the FDA for our first in-human trial, within a year, I want to be able to open that trial. Now, maybe not. Maybe it's 18 months, but it's happening. Getting pig organs into humans, it's happening, right? We are doing face transplants. We are doing hand transplants. The immune system is still fighting us, but that's all possible. So I always ask the patient, turn around and look behind you. Look at how far we've come. I know for your mother, yourself, your father, each individual, it's always gut-wrenching because it didn't happen in time for. But look where we're at. I mean, CRISPR, the molecular scissors, have approved drugs to treat genetic diseases. Okay, that wouldn't have been possible. But remember, for your audience, hundreds of thousands of people are cured with stem cell transplants, called bone marrow transplantation. You have a single cell called a hematopoietic stem cell, blood-forming stem cell. All the red and white blood cells come from a single cell. You give someone bone marrow that's a match, and it replaces them. That's every day patients are cured. Just remember that. There are examples of stem cells, and everyone's like, I know, but my dad's paralyzed. I want him to walk. Okay, that's a tough nut, but we're getting better. What if I said, with an exoskeleton, you can be up and walking? Everyone's like, what? You know, you know what I'm talking about. They don't realize how things have moved forward. And for your audience, you know, I get it. It's never fast enough, but it's the ability for the other disciplines. Like at Stanford University, I have a co-appointment in bioengineering department, co-appointment in material sciences. So bringing electrical, chemical, mechanical forces to bear on the body, and then bringing them to the body, and then bringing them to the body, and then bringing is a good thing when we harness it. So it wasn't just the white coat in a room. Discoveries are made by teams working together, and then massive analysis of data. That's all possible now. I'm not saying AI is here to change everything, but it's made my job easier to look for key genes that I wouldn't see manually. So I think it has been frustratingly long. I share that. But I can tell you that we're close. so many fronts. And your patients, five years from now, my guess is you're going to be doing operations very differently because of what you can do now.
[00:49:01 --> 00:49:33][Fan]
Yeah. And that's great. I couldn't actually agree more. Like at one level, the pace can sometimes seem like it's really slow, but there is so much, you know, investigation and work that needs to be done to establish sort of the safety and effectiveness and to develop new treatments. And yet at the same time, if we look back at all of our lives, even going back 20 years, for example, we're at a completely different place. Completely different world. And there's so many avenues where, you know, not only in health and medicine, but in technology, so many areas of our lives have been transformed. And that's exactly what's happening with sort of regenerative medicine.
[00:49:33 --> 00:50:53][Longaker]
Well, and I think if you're a plastic surgeon, surgeons don't have their own organ system. We joke skin and its contents. Well, skin and its contents could be with the neurosurgeon or the heart surgeon. We're trying to solve problems all over the body. We see the impact of the diseases differently than that organ-specific person. Right? So I think plastic surgeons are problem solvers, and no one's more frustrated than a plastic surgeon when they can get a reconstruction, but it doesn't look like normal tissue. Right? That's what you want. You want to establish normal. Yes, the hole's filled, but it's not filled with light. We always want light to replace light. But think of where we were 20 years ago. If I said we were doing face transplants, you just said, what? If I'm going to do a hand transplant, you just said, what? If I'm going to do a hand transplant, you just said, what? So believe me, it's coming. And the FDA is not the worst, three worst letters in the world. It's actually the safest, most rigorous body in the world. And it's also very frustrating. But you know what? I wouldn't have it any other way. But we are going to get scar-free healing into the market in the next few years. It's already been 37. It's not going to be a lot more. That would be unacceptable. And I know patients are frustrated. I'm frustrated.
[00:50:53 --> 00:51:09][Fan]
Yeah. That's so tremendously exciting. And when that happens, that will be such a big advance for all of us. Now, I wanted to ask you, what are you most excited about the future of stem cells and regenerative medicine, aside from all the things that we've talked about already?
[00:51:10 --> 00:54:58][Longaker]
So I think being able to move tissue around and having it survive, most of your patients don't realize if I suck out fat and put it somewhere else, it's really without a blood supply. And it's unpredictable. I mean, I don't know how much it'll survive. Do I routinely have to put twice as much in? That's frustrating for the surgeon. When you do a facelift, if you didn't know how it was going to come out, that would be a nightmare. Well, with things like transferring fat to plump something out, we don't know if it stays. One thing we know, if the patient gains 50 pounds, that will proportionally gain weight. So we have to do a better job of being able to modify the transplanted tissue in the case of fat transplant to be just what we want it to be. And that's what we're And not more and not less. Because right now, it's unknown. And you have, you know, in the last 10 years, you have a feel for it. But your first five patients, you didn't know the lip or the cheek. I mean, these are, you know, and patients are unhappy and you're unhappy. Now you have, you know what that is in your hands. But I want to make it very predictable on how much tissue survives. Because most patients don't realize if I take fat out of the body, it's actually not, it's not going to be as good as it used to be. So I think it's a good idea to do a better job not going to survive, doesn't have a blood supply. And when it goes back in, it has to recruit a blood supply before it dies. So it's a race. But maybe we're putting things in there that maximize the probability of it'll, it'll be predictable. So I think you'd be able to contour anything without a foreign body, and it would be predictable. What surgeons want is predictable result. That's what patients want too. And I don't think we're quite there yet. We're better. But I think there's some things we could do to help you with tissue transplantation that gives you a predictable result. So if you could make an incision anywhere you wanted, and you could modify contour any way you wanted without having problems of blindness and injections around the eyes, etc, you'd be happy, the patient would be happy. But I think the real thing is, you know, we're not Benjamin Button, right? We're not getting younger during this podcast, right? One could argue, as a male, you know, my prostate is enlarged during this, you know, I mean, think about it. I mean, I'm not a man, I'm not a woman. I'm not a woman. I'm not a what aging is on the margin. So how do we tap into looking younger? But that's a complex thing, because we're exposed to sun, right? People aren't helping themselves by having actinic damage. Now, I'm married to a dermatologist. So the biggest oxymoron in our house is a healthy suntan, right? So we have to do a better job of preventing damage on the margin every day. And then what can we do, with stem cells for skin to rejuvenate the skin? But it's more than that, because it's sub-Q tissue. You know what aging is in the facial skeleton, it's not just the skin. So I think we can do that. But we have to really understand how to modify the skin in terms of keeping it from aging. How do we keep the sub-Q fat? And what happens to the skeleton? If we knew those things, we could have a patient with the same contour that they, and we're not there yet, but we're not far off. I don't think, I think facelifts are going to be around for a long time. I think they're going to be different. And I think tissue transplantation is going to be really much more of a part of it. The facelift is the base, but then for that patient, but the surgeon just wants to know, is it predictable? We're not there yet, but I think we're, think of how you do a facelift today versus your first year in practice. You've incorporated things that work and don't work. And I'd like everyone to have your experience, your financial ability at the beginning because of what we're doing. And we're not there yet.
[00:54:59 --> 00:55:25][Fan]
And so if we want to get really practical for people that are listening, like, you know, if we look at the state of the world in 2024, you know, do you think there, is there a place today for stem cells in the areas of aesthetics, you know, regenerative medicine, and even people who, you know, so people who want to look younger, people who want to feel younger and maybe slow down or turn back. Do you think there's a place for stem cells today?
[00:55:26 --> 00:56:38][Longaker]
Not exactly. Right. They're just not quite there because I want to look younger. I want to feel younger. I think if people in general, they won't, they won't like this answer. If you don't smoke and you keep your weight down, those are two gigantic things and try to stay out of the sun. But, you know, patients get stiffer as a function of time. The musculoskeletal thing's not pleasant. They're not dying, but they're not happy. So I think if people maintained their weight, minimized their sun exposure and stretched every day, that would go a long way to the feeling that you're slowing down. What you're saying is the Holy Grail reversing. And that's going to be a bit of a long slog, but I think there are ways we can do skin tightening without surgery. We're not there yet. Probably when Fraxel came out and you had to... Crust or CO2 laser does a great job of removing the dead outer layers, but it doesn't give you the tightening you want. It'd be great if it did. I mean, patients would love it, but it didn't work. So it's going to be a combination of new technology like that, how to keep tissue surviving, and then minimizing the damage each day.
[00:56:38 --> 00:56:56][Fan]
Super exciting. You know, it's been a wonderful discussion. Thank you so much for, you know, for coming and having this conversation. And I look forward to more.
[00:56:56 --> 00:56:56][Longaker]
Absolutely. Thank you for having me.
[00:56:59 --> 00:57:37][Fan]
To our listeners, thank you for joining us on this journey into the world of stem cells.
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