Exosomes: Possibly the Key to Curing Disease

In this conversation, Dr. Michael Heke and Mark Chenoweth discuss the transformative potential of exosomes in regenerative medicine and aesthetics. They delve into the science behind exosomes, their applications, and the importance of proper sourcing and manufacturing. The discussion also addresses common misconceptions about regenerative treatments, the future of exosomes in aesthetics, and their promising applications in hair restoration and pulmonary health. The speakers emphasize the need for patient education and realistic expectations regarding treatment outcomes, while also providing practical tips for using exosomes effectively.

Dr. Michael Heke

Linkedin-Michael Heke

https://resilielle.com/

Mark Chenoweth

Email:

mark.chenoweth72@gmail.com

Instagram: 

Aesthetic_Pro_FL

Aesthetic_Pro_IL

Amy Ingle (Sweetface Injector)

https://linktr.ee/sweetfaceinjector

Takeaways

•               Exosomes are tiny bubbles secreted by stem cells that aid in cell communication.

•               Proper sourcing and manufacturing of exosomes are crucial for their effectiveness.

•               Exosomes can significantly boost collagen production and reduce inflammation.

•               Regenerative medicine treatments take time and are not instant fixes.

•               Misconceptions about regenerative treatments often lead to unrealistic expectations.

•               Exosomes have potential applications in various medical fields, including aesthetics and pulmonary health.

•               Nebulizing exosomes has shown promising results in improving lung function.

•               Exosomes should be stored properly to maintain their stability and effectiveness.

•               Patients should be informed about the origins and safety of exosome treatments.

•               The future of exosomes in aesthetics looks promising, with ongoing research and applications.

Titles

•               Unlocking the Power of Exosomes in Regenerative Medicine

•               The Future of Aesthetics: Exosomes and Beyond

Sound Bites

•               "Not all exosomes are created equal."

•               "Exosomes are the future of aesthetics."

•               "Start using exosomes early and often."

Chapters

00:00

The Landscape of Exosome Therapy

13:54

Regenerative Biotherapeutics: Future of Healthcare

18:40

Addressing Patient Concerns

25:06

Misconceptions in Regenerative Medicine

29:49

Exosomes in Aesthetic Medicine

39:35

Innovative Applications of Exosomes

44:23

Final Thoughts and Tips

Transcript

Amy Ingle (00:00)
Mark Chenoweth is an independent aesthetics consultant and regenerative medicine strategist, helping medical spas and wellness clinics bring next generation biotherapeutics like peptides and energy-based devices into their practices. Through his platform at Aesthetic Pro Florida, he trains clinicians nationwide on science-driven regenerative solutions that improve patient outcomes, boost profitability, and elevate the overall patient experience.

Dr. Michael Heke a PhD veteran and stem cell and regenerative medicine leader, has over 20 plus years spanning pharma, academic research, clinical translation, and biotech entrepreneurships. Dr. Heke reigned at the Rockefeller University and later served in a senior role at Stanford University. He has led major multi-center clinical trials, coordinated large-scale EU research consortia, and co-founded multiple startups.

Today he serves as an executive scientific and operational leadership role at the Crowley Center for Regenerative and Biotherapeutics, advocating and advancing best in class allogenic stem cell and exosome technologies for clinical aesthetic and therapeutic applications.

Amy Ingle (01:12)
Welcome to Glow Up and Get Real. I'm the Sweet Face Injector and today we have Dr. Hekka and Mark Chinnwath and they are going to speak about exosomes, PRP, Wharton's jelly, you name it. So let's get to it.

Amy Ingle (01:29)
Can you both share your journey into the field of regenerative medicine and what inspired you to pursue this path?

Michael Heke (01:38)
Yeah, maybe I can start. So I did my PhD in stem cell biology. I started in stem cell research over 25 years ago. And so back then it was still a little bit controversial and it was a big deal, but it was obviously.

coming with great potential and possibilities and I soon became fascinated by the clinical translation of research into medical applications. So that's what I focused on, ⁓ learning as much as I could in the field of basic research but then ⁓ seeing how that could fit into the real world with all its potential and promise.

Mark Chenoweth (02:11)
that.

Okay.

Michael Heke (02:18)
It is ⁓ over 20 years ago that I actually started and became part of the first clinical trials of stem cell therapy in then patients suffering from heart failure. And that was quite successful. And that was utilizing the patient's stem cells derived from their bone marrow. And that worked quite well. But obviously all those patients were a little bit on the older side,

Mark Chenoweth (02:21)
⁓

Michael Heke (02:46)
had comorbidities.

So you basically had to work with what you got. And it was always a dream to have an off the shelf solution for stem cell therapy. And that's where we are now. That's why I joined the company that I'm currently the CSO for. We established such an off the shelf solution for stem cell therapy, manufacturing them from the youngest stem cells you can get your hands on. ⁓ The Wattons jelly of the umbilical cord.

and they are new privileged and they are very potent. Their job is regeneration and repair. They have just finished building a new human, a healthy baby. And we harness this potential and this ability and capacity towards other fields in aesthetics and cosmetics as well to achieve rejuvenation. And we have seen fascinating results ⁓ by it.

Mark Chenoweth (03:23)
after that. ⁓

Okay. Okay. ⁓

Michael Heke (03:43)
Back then, we thought stem cells would be the ones doing it all, but it turned out that it's actually mostly through exosomes. So exosomes are tiny little bubbles that get secreted by those stem cells and they communicate between cells. And there are tiny little packages that contain all the building blocks and the genetic information

⁓ for a cell how to fix itself.

how to reprogram and even rejuvenate and return to a more youthful state. So this journey started back in the controversial days of stem cell therapy ⁓ through an overwhelming body of evidence that things actually do work and hexazomes are the new evolutionary step in stem cell therapy that we can utilize not only to address medical issues but also to rejuvenate eventually.

Mark Chenoweth (04:21)
Thank

Thanks

Amy Ingle (04:38)
What about you, Mark? How'd you get involved?

Mark Chenoweth (04:41)
Yeah, so mine's probably a little bit different, probably less scientific back, but mine's more of being on the consultant and sales side of things and calling out med spas and dermatology and plastic surgeons, wellness centers. And it was probably, I don't know, seven or almost 10 years ago now that, you know, it all started with, you know, I think the first initial introduction to regenerative treatments into the

aesthetic world was like PRP. If you remember back to like the vampire facial and Kim Kardashian kind of made that famous. so, you know, at the time we were selling like lasers and, and, know, micro needling pen, it just came out. So we're all pretty intrigued, but kind of confused at what this new, you know, platelet rich plasma was and how it, it was, you know, how it was generated. then as we got into that, I started, you know, I did pick up a

PRP line and had some experience with that. And I got to see firsthand how regenerative treatments kind of really boosted the results of treatments. And then I was introduced shortly after that to the exosomes. And I really felt like, you everyone's thought stem cell therapy was kind of only for the rich and famous and that eventually maybe that would become affordable for the, for the common, ⁓ you know, patient that comes to a med spa, but, ⁓ exosomes were kind of that, that key that like,

Dr. Hecke says, ⁓ you know, the stem cell is obviously the workhorse, the exosomes are actually, I'm sure that the exosomes are the workhorse of the stem cell. So all the messages and things that the stem cell wants to communicate to those injured cells is all part of this little tiny nanoparticle messenger and it releases everything. So I was intrigued by that. made, it was affordable for med spas, affordable for the patients who wanted to really boost their results and build college and build elastin. So it kind of just.

spurred on from that and exosomes have really become ⁓ a ⁓ staple product and ⁓ solution in most aesthetic practices.

Amy Ingle (06:39)
Right. But not all exosomes are the same, is that correct? Or how that they're, how they're stored or, you know, packaged and can you explain that?

Michael Heke (06:49)
⁓ yeah.

Mark Chenoweth (06:51)
Yes, that it.

Michael Heke (06:51)
There are

huge differences. PRP is a nice keyword because PRP also paved the way a little bit. It's another proof of concept how growth factors actually do work and do something. And exosomes are just way more potent than PRP because PRP is known to have anything between five and 15 growth factors, maybe.

Mark Chenoweth (07:19)
Thank ⁓

Michael Heke (07:21)
And exosomes,

if they are sourced properly, they have the whole panel of 50 known growth factors and also a bunch of cytokines and ⁓ microRNAs that constitute the genetic information to reprogram the cell. So, as I said, all the building blocks and the genetic information, the instructions, how to do things and how to rejuvenate and repair. However, these exosomes, are tiny little lip bubbles.

Mark Chenoweth (07:39)
Okay.

Michael Heke (07:51)
And for instance, if you lyophilize them, which is often done in order to preserve them ⁓ supposedly and make them shelf stable. But if you do that in the process of lyophilization, these bubbles burst. ⁓ And the reason why that is important is that when you do that, you have a shelf stable product, which is great. You can ship it at room temperature rather than on dry ice or blue ice, which is also good.

Mark Chenoweth (07:51)
you

Okay. ⁓

Michael Heke (08:20)
but when those bubbles burst, you might still have some growth factors and so on around that survived the process, but

they can no longer function as bioactive entities. So the way an hexazome works is it fuses with a target cell that introduces all its cargo, which is comprised as a set of growth factors, cytokines, chemokines, other functional proteins.

Metabolites lipids and micro-hides and that's how they actually function if you don't have a Bioactive and intact axosome then you only have those growth factors and they might elicit biologic response That's also beneficial, but then it's only transient and superficial I always liken it to let's say you have dry skin and you put on a moisturizer

Mark Chenoweth (09:08)
So, I just wanted to say that I very the support that we're getting from

the community. I'm for the support that we're from community. I'm grateful for the community. I'm support that we're getting the

Michael Heke (09:16)
If you do that, your skin looks nice and supple and everything is fine. But if you take away the moisturizer, you are back to your dry skin because the actual problem is not fixed. And that's why exosomes are so special. They are actually able

to fix the problem so that you go from dry skin to normal skin again, and that it's fixed and repaired. ⁓ If you don't have an intact exosome, then you only have like a superficial and transient or temporary.

Mark Chenoweth (09:38)
Okay. Okay. ⁓

Michael Heke (09:46)
effect but the fixing cannot be done. So that is one big difference. The other difference is like the cell source. ⁓ We usually derive our exosomes from mesenchymal stem cells and there are various sources like bone marrow, adipose tissue and perinatal tissues. ⁓

Perinatal tissues are by far the most potent ones.

Mark Chenoweth (10:08)
I'm I'm ⁓

Michael Heke (10:12)
because these are the youngest, as you call them, stem cells, can get your hands off of these. Heripos and bone marrow derived stem cells can also be utilized, they are a source, but they are suboptimal because they come from adult donors and even if you're in your mid-20s, say, and you're healthy and you're in the peak of your life, so to say,

but you

still have been subjected to 20 plus years of environmental stress and hazards, chemicals, toxins, bad food, smoking, radiation, disease and aging. So you might even have accrued some mutations over the course of your lifespan already. That's why they are less potent and also on some level less safe and therefore a suboptimal choice for exosomes. And then finally,

Mark Chenoweth (10:59)
Great.

Thank

Michael Heke (11:06)
I know I'm already talking too much, but finally there's also ⁓ salmonella

out there and plant derived exosomes and that all sounds very good, especially for those that are concerned about anything that comes from another human. But the fact is also as Mark said, they are cell to cell communicators, these exosomes. And just as we cannot talk to animals or plants, these cannot talk back to us.

So the signal transduction and the communication is less efficient or not even possible. So they don't match up with human-derived stem cells and stem cell-derived exosomes. And that's why perinatal tissue-derived exosomes are the most outstanding ones. And that's also why you should never use lyophilized

Amy Ingle (11:58)
So Marcia, tell us about your side.

Mark Chenoweth (12:00)
Yeah, if I can just add ⁓ on the sales side of things, obviously over the last probably seven to eight years, we've seen the market really get crowded with other exosome companies and products. And I guess from a provider standpoint, you just got to be careful on what's out there. There's a lot of smoke and mirrors, a lot of marketing. They get excited about it because they think they have exosomes, but you know, there's scientific ways to get these exosomes from the stem cells. And it's important to know how they're manufactured, what's in it.

how effective are they? And obviously being affordable and things like that. there's just, I did a lot of research and really feel like these age zero exosomes give you all the proof. You can pick up any box of your competitor or competing exosomes and some of them will have like stem cell condition media or any kind of like anything that's not specifically saying that it's an exosome.

You got to really kind of question that and be like, what's really in this? And is it really just a lot of debris that has some growth factors and maybe some proteins or peptides that's kind of doing the work of the product? But to kind of echo the whole concern about a lyophilized exosome, I like the analogy that actually Amy, actually that Erin had sent to me that we talked to that she said that you got to think of like a dehydrated strawberry, like.

You can't just rehydrate a strawberry and it's back to its original form. And that's very much the same case with this very delicate, bilipid layer that's on every exosome. If that gets damaged or you remove all the water from that, it's no longer an exosome. It's just, again, debris that's not gonna be able to penetrate into these injured cells and communicate to that area. yes, not all exosomes are created equal and you have to be careful with what's out there.

Amy Ingle (13:35)
Yeah, right. That's good to know. What does regenerative biotherapeutics mean to you and how is it shaping the future of healthcare? I know, doctor, you talked about using it with heart failure in the past. Tell us a little bit about that and what other diagnosis you think that exosomes can heal coming into the future.

Michael Heke (13:54)
Well, thank you for the question. I don't think there's actually a limit. What we are trying to figure out now is the best routes of application, the dosages and the treatment frequencies that are required to get best results. So that is still a black box, but that things do work. already know we have like.

Mark Chenoweth (14:00)
you

Michael Heke (14:14)
lots of case studies, you find tons of information in the literature

and it's just about optimizing and that relates once to the most suitable products that are properly sourced and properly manufactured of course. And Mark had a very good point there, there's like so much stuff out there, especially in the exosome business and I have to say that probably 99 % of all that's out there is really

suboptimal, let's say at best. There's a lot of false promises and claims and it is obvious sometimes that we see the main effort goes into marketing and with good marketing you can basically sell everything but it is important to inform yourself about the scientific foundation that a product is based on.

Mark Chenoweth (14:42)
I'm

Michael Heke (15:00)
if you ask tough questions, you will actually find some information and will be able to distinguish between

Mark Chenoweth (15:07)
I'm I'm going to talking about the of of of of of of of of of of of the importance of the the importance importance importance importance

Michael Heke (15:07)
a good product and a not so good product or snake or which is also very rampant and especially in the field of aesthetics and cosmetics. But if you talk about a disease and other conditions and apart from aging, we've seen stem cells being applied for years already for

virtually everything you can think of. now exosomes are on the forefront because they have certain advantages. They're like very, very

Mark Chenoweth (15:29)
of importance importance of of of of of of importance of of importance importance of importance of of of of importance importance of importance importance of

Michael Heke (15:36)
tiny. So they do not cause what we sometimes see in as a kind of stem cells being applied where people suffer like a temporary raise in temperature, heart rate, or these kinds of things, headaches. Because the body, even though those stem cells are immune privileged and don't get rejected by a lot of

Mark Chenoweth (15:36)
I'm to ⁓

Michael Heke (15:57)
but the body actually realizes that something is coming in force into the body that wasn't there before. So there's

obviously reactions. For exosomes, it's less the case because they are so, so tiny. And because they are so tiny and so abundant, if you manufacture them properly, you can employ them in very, very large numbers. In addition, that can cause the... ⁓

across the blood-brain barrier, which is very important and relevant for all things neurological and neurodegeneration. We have seen them applied in Parkinson's and Alzheimer's, MS, with very promising first results. And as I said, it's a matter of finding out the perfect dosage and treatment frequency, which is also dependent on the individual patient, of course.

Mark Chenoweth (16:30)
I'm

Michael Heke (16:47)
but I don't see any limitation in the application towards virtually any condition you can think of. Some

more potent than others, obviously, but things do work because everything that goes wrong is going hand in hand with inflammation, for instance, and inflammation can immediately be addressed by exosomes. In addition, they can fix things, so they can repair cells.

Mark Chenoweth (16:55)
Yeah. Yeah.

Michael Heke (17:13)
And that is always a good thing, no matter what kind of condition or indication you suffer.

Mark Chenoweth (17:22)
I think it's really just, you know, to kind of go back to your question of how it's shaping the future of healthcare. It's just, it's very exciting time. think you would agree, Amy, is that, you know, before we're, you know, even in just regular medicine, they're trying to treat diseases and things like that. Where now patients are coming to med spas and wellness centers and they have access now to stem cells and exosomes and growth factors and peptides. So you can really, you know, help people feel better from the inside out. And so that's why I think it's just.

Amy Ingle (17:27)
Mm-hmm.

Mark Chenoweth (17:50)
We're just at the very beginning with exosomes. I've really opened it up to the general population, but I think the sky's the limit. Like we're really going to be able to repair and replace and regenerate versus just getting a prescription and taking a drug to try to mask things and try to help inflammation and continue. So pretty exciting times, I think.

Amy Ingle (18:08)
Yeah, yeah.

Michael Heke (18:08)
It's

really 21st century. It's somehow similar to AI. mean, AI will change everything so dramatically and also just at the beginning.

and I think the same is true for exosomes They're like so fundamentally and profoundly different in their way how to address certain problems and makes it easier and fast and simple and all of that based on like very straightforward notions. So it is really exciting. I share that deal with Mark entirely.

Amy Ingle (18:37)
Mm-hmm.

So how do you address a concern by say a patient, a family member, a client that says, well, if you're giving me exosomes that come from another human being and it's a cell messenger, how do I know it's not going to cause cancer or increase maybe existing bad cells in my own body? How do you address that?

Mark Chenoweth (18:59)
⁓ Thank you.

Michael Heke (19:07)
Very good question and it's a very important one. So first of all, every concern in this regard should be taken very seriously. And we had those concerns too when we started manufacturing our stem cells and exosomes, because we want to be the beneficiaries of them as well, when or if that is needed. And we want that for our loved ones as well. So.

Again, it's very important to cautiously consider the original cell source that you opt for. It has to be pristine and it has to be monitored. You need to know the medical history of the donors and so on. So all of these things are very important.

Mark Chenoweth (19:45)
Okay.

Michael Heke (19:47)
As to the mode of action how stem cells and exosomes work, exosomes in particular are always a function of their cellular origin. So they actually are messengers by a particular cell to do what the cell would normally do. So virtually all cells secrete exosomes and if you take tumor cells or cancer cell,

cancer stem cell, they would also secrete exosomes.

but these exosomes have the specific task to actually promote the tumor environment. That would be very concerning and that's something we do not want to have.

So again, it's very important to ask what source do you want to use? And that's why we came to focus on H0 exosomes and stem cells, because these exosomes or these stem cells have just built a human, a healthy new baby. And that was their job to actually develop such a baby to regenerate and fix things when they are needed.

And there's another very interesting aspect about this H0 designational capacity. And that is while we undergo development in utero before we are born, virtually anything that can go wrong in doing development can be fixed. So there was a very interesting and impressive experiment like ages ago where they inflicted a cardiac infarction and red embryos before they were born.

Mark Chenoweth (21:03)
I'm I'm

Michael Heke (21:16)
And not surprisingly, what happens then, a lot of heart tissue goes down and will be replaced by scar tissue. And normally there's not much you can do about scar tissue. However, when you did this before the ⁓ rats were born, then

even the scar tissue got fully replaced by fully functional normal tissue again. So that's what we actually call H0.

Mark Chenoweth (21:30)
And So, I'm going ahead and

Michael Heke (21:41)
Unfortunately, we lose that capacity as soon as we are born. So we still retain regeneration potential, of course, that again diminishes with age, but we do have the potential for regeneration. But that potential for absolute regeneration and total repair, that is unfortunately long. But

Mark Chenoweth (21:42)
take a bit of a look at the slides.

Michael Heke (21:58)
the stem cells that are sourced from that time and these mesenchymal stem cells that we find in the umbilical cord have been produced before the baby was born. So they do have that capacity.

And that's what we want to harness. In order to do that, you actually have to limit your culture and expansion of those stem cells strictly to a very low passage number. So you cannot culture them indefinitely or else these cells will change over time rather quickly, spontaneous differentiation, could be mutations over time and contaminations. So we want to keep them pristine and that's why

That's why we, for instance, we limit our passages to expand the cultures to four passages that is commonly understood in the scientific community and also postulated by the International Society of Cells and Research to be the limit. After four passages, we can be reasonably sure that 99.99 % of all cells are identical with the ones we just harvest.

Amy Ingle (22:39)
Hmm.

Michael Heke (22:58)
Low passage numbers is very important. The right cell source is very important. Then I mentioned we utilize Wharton's jelly. Wharton's jelly is the gelatinous substance or tissue in the umbilical cord that makes it like crunchy and sturdy. There are other perinatal sources like placenta, umbilical cord blood, amniotic fluid and so on. They're also good, okay, but they're not as good as the Wharton's jelly. So even among the perinatal tissues.

Mark Chenoweth (23:15)
I'm going with a couple of So, the first question is, how do

Michael Heke (23:26)
Wartons jelly is by far the best. One of those reasons is that ⁓ the stem cells in the Wartons jelly are even protected by maternal contamination. So you won't find any vaccine residues in there, which is a concern for some

Mark Chenoweth (23:27)
think the address this issue? And then, the second question is, do you think government to this issue?

Michael Heke (23:43)
people. You don't find any DNA in there, which would potentially cause replication and so on. So here we go, Wartons jelly, HCO stem cells.

are the most pristine ones, the youngest ones, they the most potent ones, they do not carry the DNA, they are not able to replicate, are acellular, they are not living entities, so they cannot change anything. And the way it works is like they can only do good, right, by their designation and by their cellular origin. So if damaged cells take them up,

they will get fixed and return to a new youthful state and bad cells or like if you happen to have a tumor or something, they cannot utilize them in a way, if that makes sense. So there's virtually no concern whatsoever that they could either cause or promote cancer. And the concern, especially with cancer, relates to something much older when it was found that ⁓

Mark Chenoweth (24:18)
and they have a lot of with you and I that's great way get out of this hell of a lot of work. I that's a great get out of I a get out I of a lot of work. I think that's a out of a lot of of hell of think of I

of lot of

Michael Heke (24:45)
Blue important

stem cells like embryonic stem cells and IPS cells occasionally cause teratomas, which are benign tumors, just because they are so potent that they're hard to control. We don't want that. That's why we're using mesokinous stem cells. They're only multipotent. They can virtually do anything we want them to without causing these kinds of problems.

Amy Ingle (25:06)
Okay, interesting.

Mark Chenoweth (25:07)
Yeah, and I obviously did a great job of explaining it. I don't know if I can add much more, but on the layman's terms, it's good to have the scientific version and then the business side or the sales side or consultant side. But when I meet with providers and patients, I typically just explain to them that there's really no risk there because like Mike mentioned, they are completely a cellular, which means to explain that is there's no cells in them.

Amy Ingle (25:11)
Mm-hmm.

Mark Chenoweth (25:31)
something doesn't have a cell that can't transfer anything from the donor patient to the end user. So it's always 100 % very safe and effective. hopefully that helps you.

Amy Ingle (25:43)
Yeah, that's—you explained it very well. Thank you so much because, you know, I've heard different scenarios of why exosomes are so great, but I mean, you told us scientifically why and I really appreciate that. So I can explain that now to my patients easier. So I appreciate that so much. What are some misconceptions about regenerative medicine that you'd like to address?

Mark Chenoweth (26:05)
Well, we talked about someone being that all peptides are created the same. Obviously, we've gone into that. I think people think that it's going to be a quick fix. think that we're very quick on saying they're used to Botox. It's going to set in in 24 hours. Regenerative medicine takes time. I think it's a biology. So we know that collagen takes about 8 to 12 weeks to develop.

Michael Heke (26:09)
Yeah.

Mark Chenoweth (26:27)
The two biggest benefits that I think that exosomes bring besides cutting the inflammation down, cutting the downtime in half on most of these procedures is that you're really boosting the collagen and there's been studies that collagen and elastin and there's been studies that show like a 600 % increase in collagen production when you add exosomes. But again, it's not overnight. they're just gonna slowly, patients are gonna see that their skin starts to feel better, it starts to look better. But that's one, I guess.

misconception is that they think they're going to throw some exosomes or stem cells or PRP on and then instantly, I think the instant gratification is they see that that redness has gone down, but really the main regenerative side of it hasn't even kicked in yet. So I think that's one of them. don't know if Mike has another one.

Michael Heke (27:08)
No, that's a very good point. And if you compare it to other things like peptides, vitamins and all these kinds of things, they are good or individual growth factors. PDGF is like, you know, hyped beyond belief and they are all good things, but they're just like one, one particular aspect of a whole complex system. You also have to imagine that our body is constituting each cell of like roughly 20,000 genes.

and they are all expressed at a certain level. And you can imagine that if you throw in like one growth factor or one peptide or even like a handful, they do something, yes, because they are relevant, but they can only do so much. And as it always is in regenerative medicine or most of the time, it's mostly symptomatic treatments. So it's palliative. They give you a temporary fix, ⁓ improvement.

but it won't last and exosomes or stem cells are the only means by which you can actually fix things. And it's a good point that Mark said, like it might actually take some time. So if you aged like we all have for a few decades, know, now us being in the thirties, know, we don't look like being in the twenties anymore. If you want to return to a more youthful

Mark Chenoweth (28:08)
you .

Michael Heke (28:30)
look and so on. It takes a couple of applications and we have seen that we did

a 100 person clinical trial for skin rejuvenation with our exosomes after micromethylene and we had very good results. But it was also apparent that people on the younger side in their mid-30s, low to mid-30s, seemed to benefit more from it. So they had a more visual impact of the three treatments that were given.

Mark Chenoweth (28:36)
Thank you.

Michael Heke (28:57)
as opposed to those

people that were a little bit advanced in age in their 60s. And that obviously makes sense because if you are a rather 60 plus year old, it takes more time to shave off than for somebody in their early 30s. So it all makes sense that it will take time. And then of course age keeps progressing, right? We cannot prevent aging per se.

Mark Chenoweth (28:59)
So, I'm to presentation. ⁓

Michael Heke (29:25)
but we can slow it down and we can alleviate

Mark Chenoweth (29:29)
That is

Michael Heke (29:29)
certain downsides of aging. And that's why we maintain these kinds of regimen over time to make sure that we do the best we can. Similar to working out, you you have to work out and at advanced age, you actually have to work out a little bit more, you know, it hurts a little more than that.

Amy Ingle (29:49)
That's right. That's right.

Mark Chenoweth (29:50)
true.

Amy Ingle (29:51)
That's right. Well, how do you see the relationship between exosomes and aesthetics medicine evolving in the next five years? I know right now it's really big to have exosomes in a skincare product like a cream or lotion. And as we, as you discussed earlier, those are not very therapeutic. So if you were to inject the exosome, say in the face, opposed to applying it,

Mark Chenoweth (29:57)
I'm I'm going to be talking the that we're to So, I'm to talking about the new that we're to So, So, new we're going So, new

we're going So, So, going new So,

Amy Ingle (30:18)
Do you see that in the future or is that being done now?

Michael Heke (30:23)
see that in the future as the

most promising approach. Everything topical is doing fine, but it's the cosmetics, aesthetics industry and you you get away with a lot of stuff that's why you have so many exosome providers. If you think about it regenerative medicine wise then the hurdles are much much higher.

Mark Chenoweth (30:26)
Okay. Okay. ⁓

Michael Heke (30:48)
You can apply those. There's the right to try, the compassionate use, and there's

a mechanism ⁓ allowed by the FDA that's called expanded exosomes and so on. So you have various means to actually employ both stem cells and exosomes for medical applications today. But most physicians are not very familiar with it or they're a little bit concerned about their malpractice insurances or...

the FDA hasn't specifically approved things and it cannot be done quickly because the reason why the FDA stalls on both stem cells and exosomes is that it is hard to normalize things. You have to afford batch to batch consistency. That means like your manufacturing standards have to be extremely high to provide a good product and

Mark Chenoweth (31:17)
I'm going to go start the presentation.

Michael Heke (31:38)
It's not rocket science, but it's really tedious and diligent

work you have to do. And because most providers cannot or don't want to do that, know, your products out there are so-so. And that, of course, makes the FDA very wary. Arguably, there's Big Pharma who's less interested in this entering the market because they do not want to fix things. They want to treat people because that's where the money is.

So it goes all over the place. But coming back to your question, injecting, we also work on this because sometimes it's like this, I don't want to say gray zone, but there's this overlap between an aesthetic application and medical application. To give you an example, we successfully treated scars. So scar prevention is one thing and even scar reversal is possible.

And then it's a very interesting thing. If you say, I want to improve the appearance of a scar, then it's a static application and you can do it. If you say, I want to treat a scar, then it's a matter of application. Even if what you're doing is the same thing, it would be just by the word and it would be different. Or if you take microneedling, if you do a microneedling first and then exosomes, it's aesthetics. If you were to put on the exosomes first and then microneedle over it,

Mark Chenoweth (32:30)
I'm going to take a few minutes to talk about importance of

work that we do. ⁓

Michael Heke (32:53)
it would become medical application. So it's a little bit absurd at times, ⁓

but those are the things that we have to observe. That's by the way why we have two companies, Regenerale is the parent company who manufactures everything according to FDA guidelines, has a New York State tissue bank license, which is one of the hardest to get, CGMP and everything is done in clean rooms and so on to provide a medical grade product.

And this product is also utilized by all cosmetics. That is Résidier. So it's virtually the same product. Everything is medical grade. So for cosmetics is arguably an overkill, but we believe in it because if you do a micro-needling on your face, you have like an open wound. So whatever you want to put on there better be medical grade ideally. So we believe in that and it would be also okay to inject it, but

Mark Chenoweth (33:27)
Okay. Okay.

Michael Heke (33:48)
If you want to inject it today, it has to be regenerale. If you only apply it topically, can be reserved. It's

just regulatory wise, these are things that are necessary in place. But yes, mean, obviously when you inject, have seen that in hair restoration, for instance, that microneedling plus exosome is very effective. If you inject it, it seems to be somewhat more effective and you might...

might need lower dosages, which makes it more affordable. And then you just have to live with a downside of a more invasive procedure maybe. But there's a variety of things how you can ⁓ team it up with adjunct therapies like CO2 guns and all the things that are out there that you can combine with exosomes with no need to really inject. But it will come and it will be very exciting. It it more...

Mark Chenoweth (34:20)
I'm to a minutes get done.

Michael Heke (34:38)
I think.

Amy Ingle (34:40)
Yeah. Well, you brought up hair restoration. There's a lot of medical spas that are doing this

now. ⁓ One of the methods is to apply it to the scalp and then ⁓ push it through with ultrasound. Another is to inject it straight. And then there's a third way of microneedling and applying it. One of my questions to you is if you are injecting it, which is something that we do in our medical spa,

Mark Chenoweth (34:45)
So, I'm going to first So,

Amy Ingle (35:05)
What is the minimum, the smallest size needle that does not

destroy the exosome? Because I know like with PRP, we need to stay at 27 or above the gauge. Do you know what that would be?

Mark Chenoweth (35:10)
Thank you.

Michael Heke (35:19)
There's no limits. The exosomes and the reason why you do PRP is a little bit different because it's plasma that you also want to utilize. actually, when you talk about hair restoration, we have seen amazing results, not in the US, but actually our people in Pakistan, there's like different regulatory frameworks there

and they can inject exosomes, even our topical ones and they often combine it with PRP and

What happens then, the plasma and the PRP promotes like a fibrin mesh of sorts that keeps those exosomes in place. So it seems to be even more efficacious than exosomes alone. So the combination is great. When you inject it, you need lower dosages because you're more targeted.

all the adjunct therapies we are aware of, which is any kind of operation really works. Microneedling in particular, because we have like these hundreds or thousands of micro channels that allow the exosomes to penetrate a little bit deeper into the skin. Same for those CO2 guns, they seem to be very effective, although they might destroy part of the exosomes.

We don't know, there's like things like intubasonic. I'm not so familiar with all these et cetera therapies, but all of them work to one degree or another and surprisingly well. You could even utilize exosomes just by itself, but then because they have the ability to actually penetrate the skin just as it is by massaging them in, but any kind of abrasion or getting deeper into the tissue is definitely helpful to have a better experience.

Amy Ingle (36:56)
Okay, all right.

Mark Chenoweth (36:56)
Yeah, and

if I could just add a little bit, Amy, you know, when I was selling PRP systems, I think a lot of the providers were just used to injecting PRP because the PRP molecules are so large, you have to get them down deep with a needle. And then once exosomes kind of came to the surface and they realized how much more effective they are because they have way more growth factors in them than, you know, the age-dependent

Amy Ingle (37:11)
Mm-hmm.

Mark Chenoweth (37:19)
effects that affect the PRP. We found that, you know, the micro channels on the micro kneeling pen are plenty large enough to get these nano sized particles down to where they need to be. And exosomes inherently are attracted to inflammation. So you just need to create that injury, that inflammation, and the exosomes find those hair follicles, wake them up. And we've just found, I've found personally that, not personally, because these follicles are dead, but working with my providers,

We just saw better results with the exosomes and a much more comfortable treatment for patients that you really don't have to inject them anymore. You can just create that 0.5 millimeter to maybe 0.8 depth that is very tolerable. And you just make those injections with the pen and then topically apply the exosomes. It's been a nice change for the hair restoration market for sure.

Amy Ingle (38:08)
Okay. Now, I know it was discussed, doctor, that putting the exosomes in like a PRP plasma base, it might increase and be more beneficial. Would this also be ⁓ beneficial in applying topically?

or straight, straight XOs. Yeah.

Michael Heke (38:24)
Probably not. If you go just

topically, you basically don't need PRP because you need it if you would like deeper into the tissue, then it's very beneficial. But for topolayification, exosomes will do. And PRP, the one downside of PRP is also somewhat invasive. It's a blood draw. You have to do the procedure to actually get your PRP and then...

Amy Ingle (38:33)
Mm-hmm.

to straight.

Michael Heke (38:47)
you have what you have and you never know what's inside really. So it's completely a black box.

Mark Chenoweth (38:51)
Right. our platelets

Amy Ingle (38:54)
Right.

Mark Chenoweth (38:56)
are inflammatory. You know, when you put PRP on someone's...

you see them light up where exosomes are that anti-inflammatory response. So it's the total opposite, much more effective product with exosomes, think, personally.

Amy Ingle (39:07)
Right.

Michael Heke (39:07)
And

Mark had a good point, like microneedling is the most prominent candidate. So we inflict micro damage and micro inflammation. That's why you are all red. And that triggers, of course, endogenous repair mechanisms. So the skin tries to repair the problem. And then you provide those exosomes and they are happily taken up with great appreciation to support this repair mechanism and amplify it dramatically. So that's why it looks so well.

Mark Chenoweth (39:27)
Exactly. ⁓

Amy Ingle (39:33)
Mm-hmm.

Yeah.

What about nebulizing exosomes? Tell me a little bit about that.

Michael Heke (39:40)
Yeah, it's often done ⁓ for at-home care that you have a little nebulizer or atomizer you need for like skin or for inhaling. Inhaling, also done. If you have any condition that's like pulmonary with your lungs or so.

Mark Chenoweth (39:41)
Thank

Amy Ingle (39:48)
inhaling.

Mark Chenoweth (39:55)
I'm talking about

Michael Heke (39:57)
the nebulizer is a go-to. My mom is suffering from COPD and she is fairly advanced stage. Now that she's end stage. And we tried the nebulizer and exosomes and at first it was not very effective. We tried a hundred billion and then we realized we have to go

Mark Chenoweth (39:57)
the impact of COVID-19 on I want to talk about the impact of COVID-19 I want to impact of COVID-19 I want impact COVID-19 want community.

Michael Heke (40:15)
up.

250 billion actually helped her dramatically. COPD is a progressive disease. You cannot reverse anything about it. It will only get worse. It will never get better. And yet when she underwent these nebulizing treatments, her lung function improved from 30 % to 40%. And her doctor was flabbergasted and was wondering what she did, how she could possibly improve.

and same like all these like symptomatic things like the deep chested mucus that can never really come up, all of that cleared out. So she had a dramatic improvement. If it can be reversed, that's a different story. It's really about like the frequency of treatments, dosages and so on. So it's very tricky, but it does work. So for everything pulmonary, I would advise nebulizing.

Amy Ingle (40:59)
Mm-hmm.

Mm-hmm.

Michael Heke (41:07)
And then for everything neurological, cognitive function and so on, you should use a nasal spray. We have seen simple nasal spray application having major effects on a baby with cerebral palsy. So she was just getting nasal spray three times a day and she started being alert and responding to her parents. She was at some point able to stand and take steps and so on.

was unbelievable and also utilize it towards various conditions now in MS, ALS and all these neurodegenerative diseases, Parkinson's. And if you combine that with regular IV therapies, then it's the best of all worlds. We are currently entertaining a preparation of a large clinical trial with NFL players, former NFL players, to address all these downsides, the effects from...

Mark Chenoweth (41:41)
I'm

Michael Heke (42:02)
commonest concussions they have to go through. And it's very exciting to see what the outcomes are.

Amy Ingle (42:08)
Yeah, that

is exciting. ⁓ that is really… I can just think of all my friends and my family and my patients that would benefit from exosomes, nasally and inhalation.

Mark Chenoweth (42:09)
⁓ Okay.

Michael Heke (42:14)
Yeah. ⁓

yeah, basically

so you don't have to wait until you have any condition. If you have like a nasal spray bottle at home and like you utilize like one, two, three times a day it will definitely do something for you.

Amy Ingle (42:33)
So if you were just to receive the age zero, it comes in a five ml and you put that in a nasal spray, but how long can it sit in the refrigerator?

Michael Heke (42:37)
Mm-hmm.

We have seen it stable for over a year. it's oh, yeah So we typically don't advertise it because as a manufacturer you want to err on the side of caution So we typically give out different expirations dates, we know for sure that we have tested our exosomes After staying a fridge for over a year and they were perfectly fine. There was no degradation in terms of integrity

Mark Chenoweth (42:45)
Mm-hmm. ⁓

Amy Ingle (42:47)
in the fridge? Wow.

Michael Heke (43:10)
or bioactivity. We have even seen it like over 30 days at room temperature without any loss, apparent loss. So they're supremely stable. are delicate as Mark pointed out in one regard whenever it comes to lyophilization, for instance, but they are not as delicate as if they would immediately be destroyed or go bad when you keep them in the fridge rather than a freezer or even at room temperature.

Mark Chenoweth (43:20)
.

Michael Heke (43:36)
It's nothing that we would comment, but it's always if you get those exosomes, keep them in the freezer until you're ready to use them. If you started to use them, keep them in the fridge. Or if you have like your nasal spray at home, for instance, then of course you keep them in the fridge and not in the freezer. You don't want to throw them all the time. And for as long as you avoid repeated ⁓ freeze, throw cycles, and I even find

Amy Ingle (43:55)
Right.

Michael Heke (44:03)
When we ship them on dry ice and a package gets delayed and they started thawing or have been thawed, for as long as they have not been subjected to temperatures above 140 degrees Fahrenheit, they're still fine to be used. Just put them back in the fridge or freeze them again if you want to use them for longer storage. Then they're fine. So extremely stable.

Mark Chenoweth (44:15)
⁓ Okay.

Amy Ingle (44:23)
Good, wow, good to know that, great. Well, one last question. What is your sweetest tip of the day?

Michael Heke (44:30)
that is an unexpected. ⁓ Yeah, well, if you want to use exosomes, first of all, ask critical questions. Don't settle for anything that is just like making wild claims and promises. Look a little bit behind the scene. mean, that is not so sweet a tip because it's more like be prudent or ask tough questions.

Mark Chenoweth (44:31)
Okay. Okay.

Amy Ingle (44:32)
Right? I ask everyone that comes on.

Michael Heke (44:57)
always

ask for a product that comes with a certificate of conformance, that you actually see how it's manufactured, that third-party testing is done for a pristine product. So, ours, for instance, come just in saline, physiological saline. There's nothing else in there, only exosomes and saline. That's, by the way, why they are so stable, because we do not have any contaminations. There's nothing aseptic, spheruline. So, nothing can happen to that.

So that is very important as for nanoparticle analysis to see that it's really what's supposed to be in there. As for electron microscopy pictures that show that you have an intact exosome and then you can be reasonably sure that you actually have a good product. And other than that I would advise it's coming. It's certainly a revolution of what we can do.

Mark Chenoweth (45:35)
you

and I'll you later.

Okay. ⁓

Michael Heke (45:48)
start using them early, start using them often.

And I guarantee you will be aging better. You might even return a few at the clock, a few for years. And then we will all find out what the potential and what the limits are.

Mark Chenoweth (46:05)
Amy, you'll like my tip because it's short and sweet, but do you know what the cheapest collagen stimulator is on the market?

Amy Ingle (46:06)
Mm-hmm. Mark, do you have a kit?

Mark Chenoweth (46:14)
It's to smile. So if you smile, you'll stimulate collagen and that's the way it goes. So that's my sweet tip of the day. All right.

Amy Ingle (46:16)
Aww.

like it. I like that a lot.

Well, how can the listeners get a hold of you?

Mark Chenoweth (46:27)
⁓ For me, yeah, no phone numbers. For me, can reach probably best way is on Instagram. I'm at AestheticProFlorida or the abbreviation FL, AestheticProFL. And then obviously my, you want my email, I can do email. It's marked. Okay, perfect, yeah. If you put in the link, that'd be great.

Amy Ingle (46:28)
No phone numbers.

Sure. I, well, I can put the, it in link.

Yep. And what about you, doctor?

Michael Heke (46:49)
Yeah, I could refer you to my company websites or so, but both Regenerex and Resilielle in particular are mouthful. You probably will able to figure out how exactly they are spelled. So look for myself on LinkedIn. Michael Heke is my name. H-E-K-E. That's a four letter word, easy to remember, not to be confused with hickey.

Amy Ingle (46:57)
Alright.

Michael Heke (47:10)
⁓ If you want to make fun of me that works too. Or contact Amy and we'll be in touch.