A Primer on Potential Uses of Stem Cells in Plastic Surgery w/ Dr. Steve Cohen

Doreen Wu (00:01):
Welcome to another episode of Park Avenue Plastic Surgery Class, the podcast where we explore controversies and breaking issues in plastic surgery. I'm your co-host, Doreen Wu. I'm excited to be here with Dr. Lawrence Bass, Park Avenue plastic surgeon, educator, and technology innovator, and our special guest plastic surgeon, Dr. Steve Cohen from San Diego, California. The title of today's episode is "A Primer on the Potential Uses of Stem Cells in Plastic Surgery."

Dr. Lawrence Bass (00:32):
I'm really delighted to have Dr. Steve Cohen, a plastic surgeon in San Diego, California, back with us on the podcast today. He is a very accomplished surgeon, but he has also been a very active researcher in the fields of regenerative medicine, and particularly looking at stem cells, how they can be obtained from harvested fat and how they can be used therapeutically, not just in plastic surgery, but in a whole range of medical applications. So, Dr. Cohen, welcome and thank you for joining us.

Dr. Steve Cohen (01:10):
Thank you, Larry. Nice to be here.

Doreen Wu (01:13):
Stem cells have captured the imagination of scientists and researchers due to their regenerative abilities. Dr. Bass, we've all heard of stem cells and their myriad of applications in medicine and research. Why is this an important topic for us?

Dr. Lawrence Bass (01:26):
Well, let's back up for a second and talk about what plastic surgery tries to do and what stem cells are. So again, plastic surgery is designed to rebuild or regenerate part of the body that's been damaged by trauma, damaged by disease, affected by aging, or is congenitally in some way deficient. And so for a long time, plastic surgery has tried to rework body tissues borrowing from other parts of the body. Stem cells are cells that are not fully differentiated and have the ability to turn into a muscle cell, a skin cell, a blood vessel lining cell so they're cells that are not fully differentiated. And that flexibility allows them potentially to be used in the service of that plastic surgery mission. And that potential is so powerful, it's captivated the imagination of both the public and of many, many in medicine.

Doreen Wu (02:43):
And Dr. Cohen, in more detail, what are stem cells exactly? How could they be useful in medicine more generally?

Dr. Steve Cohen (02:51):
There are two types that we think about. One are your embryonic stem cells, which are pluripotent, meaning those cells can turn into anything versus adult stem cells, which basically are mesenchymal stem cells that have the ability with certain tweaks to turn into certain tissues, but still somewhat limited relative to the embryonic, the embryonic, we're years away. There are so many regulatory issues and other things we don't fully understand that that's a science that is still undergoing a lot of work in the lab. Whereas mesenchymal stem cells are widely available either through harvesting them in the bone marrow or harvesting them in our fat. And our fat has so many more of them relative to bone marrow, that that's become a very important source. So these stem cells being uncommitted, you know, can turn into other things. That's the theoretical benefit.

(03:56):
The practical benefit of using these are that they have known effects in improving blood supply, making new blood supply, reducing inflammation and repairing tissue. So for instance, as a plastic surgeon, my first involvement in this field was to harvest fat after a patient had a heart attack because we were going to take the stem cells and the regenerative cells out of the fat and inject them into the coronary artery that had been now opened up. And those cells were gonna go into the area of injury and they were gonna stabilize some of the cells that, you know, got hit in their head. But we're starting to recover, but some were going to die and others are going to get better, and hence limiting the size of the heart attack or the injured muscle. So that's my first involvement. And when you saw some of the anecdotal results, again, without realizing, without testing the genetics of these cells, because some again, are not going to be effective and others are going to be very effective, we saw amazing results.

(05:08):
We saw a reduction in the number of patients that died, a reduction in the number of patients that went on to develop heart failure because they had more muscle intact, and a reduction in the number of patients that had serious rhythm abnormalities because these cells were being irritated by low oxygen and the heart attack. That was my first introduction. And as I said, what I was convinced of is that, you know, we find amazing medications in fungi, in things like, you know, plants. And yet we ignore the human body's ability to repair itself in a complex way. So this is where we get these things. And so in plastic surgery, stem cells, unfortunately at the beginning took on a lot of hype. Everybody was marketing stem cell, breast augmentation, stem cell facelift. It was really disappointing because they were taking a highly scientific field and turning it into kind of a circus show. And that led to many of the societies condemning the use of these things. And it's been 20 years and things are just beginning to turn around where people are realizing these are going to be the future treatments that all of us are involved in.

Dr. Lawrence Bass (06:32):
So what are some of the big studies that are going on now that are starting to be done to meaningfully evaluate the role of stem cells in different medical therapies?

Dr. Steve Cohen (06:43):
Well, there've been studies by a company called Mesoblast, which are taking, these are stem cells that are called allogeneic stem cells. So these are from patients that have died and donated their tissues to medical science. You can harvest their stem cells, purify them, clean them, and make them ready to be injected. So there's many studies in orthopedics and in cardiac that are beginning to demonstrate effectiveness in certain disease conditions. And again, it may turn out that we see, you know, a huge effect in certain patients with angina of a certain variety, and we see very little effects in another group. So these are the things that we have to begin to hone in and understand.

Dr. Lawrence Bass (07:35):
So if we then turn back to aesthetic plastic surgery specifically what do you think the potential applications are for stem cells? Probably going to be obtained from fat because that's something plastic surgeons know how to do. So where, where do you see that being applied going forward?

Dr. Steve Cohen (07:59):
So I think, you know, if you look at the world landscape in the US most of what we're doing is related to anti-aging or breast reconstruction or reconstruction of various deficits. In the aesthetic world, I see most of the benefit in anti-aging using stem cells and their associated, you know, elements like exosomes and other regenerative cell populations as a means of reducing the rapidity of aging in facial tissue. So I think that's going to be something that is being done right now. And I'm sure this is a question that's going to come up. There have been some regulatory hurdles. So early on we were able to obtain stem cells using enzymatic dissociation, meaning if you take out fat, you gotta separate out those cells somehow. So how do you pluck those cells out? You would use an enzyme called collagenase and that would break the bonds of these cells.

(09:04):
And then with rinsing and centrification, the cells have a certain weight, they would fall to the bottom and they would stick to plastic and you could collect them, you could clean them further and use them for different applications. But the problem was that the FDA deemed that is more than minimal manipulation. So researchers and clinicians have had to come up with other mechanisms of basically segregating those cells from fat. So one way of doing it is to harvest the cells and to break them down by a process called emulsification, where basically you just take two syringes filled with fat, go back and forth, you gradually reduce the size of the fat, and then you pass it through small filters to collect what are called nano fat. Nano fat is unfortunately a name that's caught on, but is a type of stromal vascular fraction that is mechanically produced with a small number of cells.

(10:09):
Now, somebody comes to you and says, here's a good nano fat device. Well, not all nano fat is the same. It's like platelet-rich plasma. One device is going to yield more cells. And almost all researchers working in this have come to their point of view that more cells is better. But because the mechanical ways of making or collecting these cells retains certain cell aggregates, it's not like a pure population of cells only there seem to be more effective for certain things like wound healing. Now, with non enzymatic techniques, up until about a year ago, we're able to obtain about 40 to 50% of the yield of cells that we can get from an enzyme. So less powerful, but still potentially effective. About a year ago, again, a group that I've been working with in out of the UK, basically a group of scientists from Turkey, Israel, Switzerland, and the US have come up with a means of harvesting mechanically these cells in the equivalent amount that you get from an enzyme.

(11:22):
And that's done by a combination of emulsification to break the cells down centrifugation and certain filters that don't filter out the excess tissue, but actually downsize the fat into smaller and smaller particles until what you're left with are mainly the cells that fall to the bottom when you spin them around. And then if you take that quantity of cells that are about 40 to 50% of what you get from an enzyme, you go, well, where are the rest of the cells? They haven't disappeared. The rest of the cells are actually in the buffy coat. So if you take the buffy coat and add that to the cells at the bottom, you now get something called hybrid stromal vascular fraction, and it's an equivalent amount to what you would get using an enzyme. So we've been able to now get over the barriers of the FDA because that's mechanically produced.

(12:27):
Now, how else can you get nano fat? You can design cannulas. Cannulas are metal tubes with holes in them. You can design those holes to only collect nano fat. So you can go in and collect nano fat. It's not quite as powerful. You don't get as many cells because you haven't been able to separate as many with emulsification and centrification and adding the buffy coat, but you get about 40% of what you get from an enzyme. There are other ways of doing this, but presently hybrid SVF, when you compare it to four or five different ways of obtaining mechanical cells, yields the highest number. So as we now overcome those barriers, these stem cell facelifts, these stem cell breast augmentations will at least be more effective. But we just, again, have to understand how effective that might be is still going to be variable based on the patient's age, the patient's tissue, the patient's genetics.

Dr. Lawrence Bass (13:32):
And so these stem cell fractions that you are producing these from the patient's point of view, would be applied in a treatment similar to the way a fat grafting treatment for facial rejuvenation, facial volume restoration, or for breast reconstruction, might be applied. But the hope is that the healing behavior, the other biological effects are going to be different than fat grafting alone. Because the dose of stem cells that they're receiving and the biological impact of those stem cells is so much greater than the very low dose of stem cells that's present in an unmodified fat graft.

Dr. Steve Cohen (14:21):
Right. And also, Larry, they're going to be, you know, you kind of think of it like a menu of options. But in the reconstructive world, for conditions like scleroderma, which are autoimmune conditions associated with vasculitis and reduction of blood supply, these are going to be potentially home run therapies for these kinds of patients. You know, and the more cells, the better in aesthetics. To me it's a question of age. If you are older and you have more senescent cells, you want more of the effect of these stem and regenerative cells. If you're younger, it probably doesn't matter quite as much. You're probably getting quite the similar effects with lower doses.

Doreen Wu (15:07):
Now let's talk about what's coming down the pike. Where might we get in the next five to 10 years? What is in the pipeline, Dr. Cohen?

Dr. Steve Cohen (15:16):
Well, I think, you know, the pipeline has got a ton of these kinds of little devices and these kinds of concepts. But I think what's in the pipeline is as they become more effective and more of us adopt them, they're relatively inexpensive. So it's a matter of helping to educate the public at why they're effective and why we're using them. I would think that most doctors doing breast reconstruction on radiated breast tissue would want to use these hybrid stromal vascular fractions not so much an augmentation, but to rehabilitate the tissue perhaps even before you put a breast implant in, which in the past we wouldn't dare put into radiated tissue. So that will reduce the complexity of procedures. Two: patients that have facial irradiation for head and neck cancers, they go on to develop some pretty serious problems related to non-healing wounds,

(16:18):
difficulty with movement, because muscles become very fibrotic. Some of these treatments may reverse some of these conditions as well. So in the reconstructive world, I think these stem cell applications will become really important. You know, we may be spraying burns with cells that we collect from the patient's own fat to heal them more rapidly in conjunction with skin grafting, cranial facial abnormalities, which are associated with, again, loss of blood supply. So the tissues are not normal. We'll be able to normalize those tissues, and so the results will get better and better. You know, as time goes on. And as we begin to utilize these more. So to me, the key thing right now is getting industry to step up to the plate to find the pioneers and the visionaries like a Richard Branson type guy, but who runs a medical company and realizes that the power of this is gonna be enormous.

(17:26):
Once people start to teach this on a regular basis. Once people begin to come up with a systematic approach, and they don't go, "oh, well I do fat grafting." Well, okay, but are you getting 80% volume effects two years later because you do fat grafting? So these are the things that take kind of a lot of effort to move the mountain. And again, I think we're getting closer, but there are days where I go, "oh my God, I don't think it'll ever happen and I won't ever see this truly main mainstream." But we really need industry now to step into this arena and to realize how valuable this will be. Because fillers won't disappear. Breast implants won't disappear, but there'll come a day where we'll bioprint a breast or we'll use a cadaver breast that has been decellularized, put it in the patient, populate it with stromal vascular fraction, and we'll have a new breast that's a real breast and maybe even a functioning breast.

Dr. Lawrence Bass (18:32):
So I have a question for you. You know, in the sixties we planned to land on the moon. And at the time when that was proposed, the technology, the knowledge of technology was adequate to understand what had to be done to get there. And it just had to be engineered into a working system. And in the very early 1970s, another American president said, "by the end of the decade, we're going to cure cancer." And that was not nearly as, that was not a good bet because we didn't understand so many things about the biology of all the different diseases that represent cancer. We did not have the sequencing of the human genome at that time and so on and so forth. So with stem cells today, is it more of a landing on the moon problem where we have, we understand what needs to be done, but we have to engineer the process? Or is it still like a curing cancer in 1970 problem where we still have a lot to learn about the biology and we need some breakthroughs to make it happen?

Dr. Steve Cohen (19:52):
I think a little bit of both, Larry. I think, you know, only because having followed immunotherapy, I was at the NIH and when Donald Morton was there and the effectiveness of immunotherapy on melanoma was mild and you kind of looked and went, I don't know. I mean it doesn't seem all that dramatic. And now we're at a point where it's very dramatic and you have Israeli scientists recently, maybe a year ago, announcing that with combinations of these immunotherapy approaches, they're going to eradicate most cancers. So, or at least allow us to live with them. So I think some things just take a long time. I think that to your point, what we have to do is figure out what are the most valuable approaches. So for instance, to me, facial surgery, I mean there are very few facelifts that are done now without fat grafting.

(20:47):
When I gave a talk in 2009 in Chicago at the, not the aesthetic meeting, but at ASPS, our bigger society, and I asked people to raise their hand, "how many people are fat grafting during facelifts?" You know, probably 80% of people raised their hand when I said, "how many people are using more than 10 milliliters?" Probably 10% raised their hand. When I said, "how many people are using 50 milliliters?" Maybe there was nobody who raised their hand. Now most people are using large volumes because they recognize that to actually do a good job on a facelift is a multi-dimensional approach. It's not just lifting skin and trying to fold tissue underneath to make look like you have more volume. It's actually going right to the problem, which is the loss of fat tissue in specific compartments.

(21:46):
So as we begin to become more precise in our understanding, our treatments are getting better and better. So I would imagine that we're going to see more and more facelift patients having much longer term effects. And even with the fat grafting, as I was saying, you have a patient who is a kind of slower ager. You know, I have patients six, seven years out from fat grafting that's never used a filler again and never as needed in another treatment, and their skin looks amazing still. So how does that happen? And as we begin to understand more and more how that happens, it's hard for me to imagine not using some of these techniques with every laser I do or every kind of skin delivery system.

Doreen Wu (22:36):
Lastly, before we close, Dr. Cohen, I'd like to ask you, what should our listeners take away from today's discussion of stem cells?

Dr. Steve Cohen (22:44):
I think they should take away two things. One, it's a serious scientific effort and they're going to benefit from this. And two, you have a group in the aesthetic world that are marketing and those marketing people, you have to differentiate what is marketing and hype from what is legitimate, clinical science. I think that's a very important thing. So you wanna be with physicians that are looking at this in a responsible way, not marketing it as a means of simply, "I'm getting a lot of new patients because of this." So I think that's an important differentiation is to make sure that the hype is backed up by a more serious understanding of the field.

Doreen Wu (23:34):
Dr. Bass, anything to add?

Dr. Lawrence Bass (23:36):
Yes, I think Dr. Cohen was just talking about combining use of stem cells with surgery, use of stem cells with energy-based treatments. And it's a certainty that almost everything we do is going to be some kind of combination therapy. The ability to get the most complete correction is absolutely going to rely not on one single silver bullet, but on pushing every option at its optimum amount so that we get maximum improvement. The other thing that I think we're going to see with stem cells, there's been so much focus on getting our hands on them, separating them out from harvested fat that we haven't yet had the chance to fully investigate how we're going to control the behavior of stem cells. And part of that is just dosing, but part of it is controlling their behavior because they can change in multiple different directions. How are we going to control differentiation? How are we going to signal stem cells and modulate their behavior when they're placed in rather than just shotgunning it at the patient and hoping it sticks and acts in the fashion that we hope. So that's going to be the next phase of development as I see it. But we're going to need to be routinely working with stem cells and having them available to be able to start doing those studies in earnest.

Dr. Steve Cohen (25:18):
I would echo what you said Larry is right on. I think combination therapy is so critical for patients to understand because when patients come into your office and you ask them, "have you had any treatments?" And they say, yes, I had this laser five years ago. Immediately you realize that these patients have not been educated what lasers are there for, and that lasers are not ordinarily a single treatment, but it's like car detailing. You want your car to stay nice, you're driving it around, you're going to take care of it and you're going to need to do it on an ongoing basis. Or if you're a statue in Italy and you get sandblasted, but they put you back in front of the fountain, you know what's going to happen to your beautiful white marble. It's going to get sooty again. So as we begin to look at multiple modalities, we need to be treating sun damage, volume loss, laxity, and we're drilling down into the cellular and tissue events that are occurring with aging so that we can come up with better and better combination treatments that legitimately will alter aging. Legitimately, and that includes surgery in some cases.

Dr. Lawrence Bass (26:30):
Well, I think that's a beautiful way of summarizing it. So I'd like to thank you again, Dr. Cohen, for joining us. It's been a very stimulating discussion and we're glad that you were willing to come back and talk with us again on the podcast and contributed your expertise.

(26:48):
Thank you for having me.

Doreen Wu (26:49):
Well, this was certainly a thought-provoking episode. Thank you again, Dr. Cohen, for sharing your expertise and insightful perspective with us today. And thank you to our listeners for joining us to hear about the expanding role of stem cells and aesthetic medicine. If you think of other exciting developments or trends in plastic surgery that you would like us to discuss in upcoming episodes, please reach out by email or Instagram. We'll see you next time. This is Doreen Wu, thanking you for joining Dr. Bass, Dr. Cohen, and me for this discussion of stem cell-based regenerative medicine. Be sure to tune in next time and don't forget to subscribe to our podcast to stay up to date with all of the exciting content that is coming your way.

Speaker 4 (27:28):
Thank you for joining us in this episode of the Park Avenue Plastic Surgery Class podcast with Dr. Lawrence Bass, Park Avenue plastic surgeon, educator, and technology innovator. The commentary in this podcast represents opinion. This podcast does not present medical advice, but rather general information about plastic surgery that does not necessarily relate to the specific conditions of any individual patient. No doctor patient relationship is established by listening to or participating in this podcast. Consult your physician to advise you about your individual healthcare. If you enjoyed this episode, please share it with your friends and be sure to subscribe to our podcast on Apple Podcasts, Google, Spotify, Stitcher, or wherever you listen to podcasts.