Understand How Stem Cell Therapy & Exosomes Work
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- Nathaniel Shepherd
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1 Understand How Stem Cell Therapy & Exosomes Work DOUG SPIEL: And we now believe that when you put mesenchymal stem cells from you or from somebody else in your, say, knee space, it's not those cells that actually make up the new cartilage, or the new bone, or the new synovium, but rather, they signal through a paracrine form of mediation. These little vesicles leave, these little vesicles get picked up by cells that are already in your knee, and so, that all you're doing no matter what you put in, is creating an awake portion of a pool of resident stem cells who will then go about their work and start rebuilding structures and the like. INTRO: Welcome to the Regenerative Warrior Podcast: Doctor s Edition. One of the fastest growing regenerative medicine and anti-aging podcast in the world. Each and every Tuesday and Thursday I talk to the top experts to show doctors how to market manage and magnify their practice to help more people and make more money. Each episode is short and to the point without wasting your time with pointless conversation. Learn the skills to be successful without traveling to seminars or paying for expensive consulting fees. Are you ready? Because I am. I m Doctor Ross Carter, and it s time to start The Regenerative Warrior Podcast now. DOUG SPIEL: So, simply put, if you look back about 30 years ago, people were under the belief that if you took stem cells, these are these little precursor cells that can essentially turn into anything we thought, muscle, and bone, nerve, real structures, and the like. And you put them in your knee, or you put them in your spinal canal, you put them in your disc, we were under the belief that no matter whether they came from your own fat or bone marrow or from a young child's umbilical cord or placental-derived tissues, we were under the belief that those stem cells would essentially grow into the cartilage of your knee, into the intervertebral disc of your low back. Fast forward about a quarter century, and even the forefather of mesenchymal stem cells, Arnold Caplan, has kind of repositioned his viewpoint such that what he used to call mesenchymal stem cells is now terming medicinal signaling cells. So, we really believe right now that the cells are secreting little vesicles, little packets, the packets contain growth factors and cytokines, essentially proteins, and the messenger RNA that are the little machines that make the proteins and their packaged inside of little membranes. The membranes are derived from the parent MSC. And we now believe that when you put mesenchymal stem cells from you, or from somebody else in your, say, knee space, it's not those cells that actually make up the new cartilage, or the new bone, or the new synovium, but rather, they signal through a paracrine form of mediation. These little vesicles leave. These little vesicles get picked up by cells that are already in your knee that are almost bone, almost cartilage, almost synovium. We call those resident stem cells. And so, that all you're doing no matter what you put in, is creating an awake portion of a pool of resident stem cells who will then go about their work, and start rebuilding structures, and the like. So, rather than just utilizing cells, a number of years ago, some of the scientists thought, well, maybe it's more important just to get the signalers. And the signalers don't work unless they're in the membranes. So, the effect that you get is secondary to the fact that the other cells recognize these little vesicles and basically phagocytize them or pull them out of the solution. And then, they get internalized. In those cells, they became laying-down proteins and the like in secreting vesicles of their own. And in fact, some of these vesicles contain forms of enzymes that will actually align for portions of the DNA, which is really the genetic code, in all those cells, to start laying down some growth
2 factors and some proteins that they may not have produced in many, many years.so, you're kind of turning them into a younger better version of the earlier cells. The problem with regeneration in our bodies, you know, we're aging, and we're losing cells every day. Many of the tissues of our bodies keep up okay. And if you've aged, you're probably, your muscles are keeping up okay. DOUG SPIEL: At some point, the vessels in your muscles will start to atrophy and you'll have less capillaries. You'll sub-serve less of these nutrients to the resident stem cells of your muscle known as satellite cells. And you will lose more muscle than you start creating, right? There's a constant state in your body of anabolism and catabolism. DOUG SPIEL: When catabolism out-distances anabolism, then things go south. So, the idea here is to basically rebalance anabolism of catabolism. And if you can, maybe up-regulate the productive forces so that you can actually build forward instead of losing steps back. DR. ROSS CARTER: Okay. So, you continue anabolism and not catabolism? DOUG SPIEL: Correct. DR. ROSS CARTER: That's the whole goal. So, when somebody is doing a treatment, would you recommend they just continue to do like a maintenance kind of treatment through the rest of their life as long as they possibly can to not deteriorate? DOUG SPIEL: I think the best portion of your question, which is a very, very sensitive question is, "Does it pay the re-treat and let's see what we're treating for." We live in a society where we're trying to pay it back rather than pay it forward. I mean that, we live in a society where we treat afflictions once they've proven themselves afflictions. Very few of us are trying to congestive heart disease, stroke, Alzheimer's, cardiovascular disease before they happen. DR. ROSS CARTER: Right, right. DOUG SPIEL: So case and point, if I could decrease the inflammation of your body, I think you could make a very compelling argument that inflammation kills us. High inflammatory states are now associated with cardiovascular disease, and stroke, and many of the reasons we die is due to these etiologies suddenly showing themselves in middle age. So what if we could give something that return back the clock of time and decrease progressive inflammation? While there are some interesting predicate studies that suggested exosomes can do this. There's a very interesting study where they took specific exosomes from umbilical cord cells MSCs, little different cargo, and I take the MSCs from placental-derived tissues, but very close. And they were giving it to people intravenously through the veins, wherein the arteries, leading up to the kidneys themselves. And they did two treatments over a week-and-a-half. And what was interesting is they give a total
3 about 15 or 16 milligrams and they look at anti-inflammatory and pro-inflammatory factors. It should be of interest to you that the anti-inflammatory factors peaked to 12 weeks but stayed above baseline for 52. Meaning that if you wanted to decrease inflammation, you may make a point of treating people every 12 weeks intravenously to keep them younger. Now, you're going to reflect back to patients who just have a bad knee, you want to treat them once or twice. If the knee continues to do well, you don't need to continue to treat them every year. DR. ROSS CARTER: How long does it last? DOUG SPIEL: So that's the interesting portion to this. People get PRP treatments every couple of weeks and keep getting them because they re proteins, and proteins get denatured by your body by prophases. If I give you messenger RNA, these are little machines that get passed cell-to-cell, so that your cells will continue to cascade of anabolic activity. Over the period of many months or up to a year or more, they will continue with anabolic activity that is leading you in a positive balance. So if your knee had a cartilage defect, and you want to start fixing some of that, if I told you for the next 6 to 12 months, you'd be working towards that. And at the end of 12 months, we take a look where you are. And if you feel good and it looks a little better, do we re-treat, probably not. On the other hand, suppose you had a stroke or spinal cord injury and I treat you at day zero, and in six months, you're pretty good but you've plateaued, your strength has plateaued, maybe your dynamic studies have plateaued. And in 12 months or 9 months, you're not getting any better, you're someone who still has a deficit that you probably still want to treat. DR. ROSS CARTER: Absolutely. DOUG SPIEL: So those are cases where we'll re-treat. DR. ROSS CARTER: Hi, sorry for the interruption. This is Dr. Ross Carter. Frequently, I get asked, Who are the best companies for stem cell products, exosomes, marketing, consulting, and other products and services mentioned on this podcast? The mission of this podcast is really to provide free education for doctors in regenerative medicine and anti-aging. And after extensive research and negotiation, we ve worked out special pricing for all of our listeners, and I ve put this together in one place. To learn more, just call us at 866-9WARRIOR. Again, that number is 866-9WARRIOR or Back to the program. DOUG SPIEL: Autoimmune disease, we similarly re-treat every 6 to 12 weeks depending upon both the clinical state of the patient and what the blood work looks like. DR. ROSS CARTER: Is that through IV? DOUG SPIEL: Yes. DR. ROSS CARTER: Okay, so you IV exosomes? DOUG SPIEL: Exosomes are very safe. So whereas you've heard of people talk about clomping of cells, cells getting clot in the lungs, exosomes are 1/100 th the size of a cell. DR. ROSS CARTER: 1/100 th?
4 DOUG SPIEL: So theoretically, you can put them virtually anywhere. I put them intrathecally in the cerebrospinal fluid, I put them in discs. DR. ROSS CARTER: And what about infections? Do they ever cause that kind of a problem? DOUG SPIEL: No. So they're immunomodulatory, but they don't comprise your immune system to the extent of steroids. I don't give them to people who are on immunosuppressive therapy. If you're on an autoimmune drug which, dampens your immune system, I like you to stop it for three halflives. Why? Because you're about 10 percent or 15 percent of the activity at that point, and I think it's fairly safe. DR. ROSS CARTER: How do you get exosomes? DOUG SPIEL: We basically take placental-derived C-section tissues. We take out the mesenchymal stem cells from these, these are the earliest adult MSCs we can touch from the day you're born, they're turned adult. We plate them, we grow them and expand them. And through a proprietary method, we spin-off the DNA and the membranes, leaving only the vesicles which we subsequently concentrated. DR. ROSS CARTER: When you say spin-off, you mean like a centrifuge? DOUG SPIEL: Proprietary. DR. ROSS CARTER: That's the separation techniques, separating the cells or the mesenchymal cells kill? DOUG SPIEL: We're removing the media that is secreted, the culture media which are the exosomes and the macrovesicles. DR. ROSS CARTER: They're so small, how can you see what you're getting? DOUG SPIEL: So we have nanocytes. So nanocytes are very small type of microscopic lenses that in which we can quantify and see the actual number of exosomes. And similarly we were on third party assays looking at protein, cytokines, interleukin profiles, as well as recently, MRNA profiles. DR. ROSS CARTER: Are these going to be, higher than say, umbilical cord dealt from the beginning? DOUG SPIEL: So what you're really looking at are apples and oranges, but let me introduce this. DR. ROSS CARTER: Sure, sure. DOUG SPIEL: When you look at a lot of the labs and if you've read many of these studies, you'll realized that patients are receiving when they're talking about exosomes in the studies, they usually take an umbilical cord amount of cells, they will cure them over a period of 24 hours. DR. ROSS CARTER: Cure them and DOUG SPIEL: They ll grow them and expand them. And over 24 hours, they will then milk out whatever the exosome will brought this or the secretions.
5 DR. ROSS CARTER: Okay. DOUG SPIEL: In 24 hours, in a simple secretion, a million cells will secrete about a 100 micrograms of exosomes. DR. ROSS CARTER: A million mesenchymal pure, right? DOUG SPIEL: Yes. DR. ROSS CARTER: Okay. DOUG SPIEL: When we give you a 5 ml vial, we re giving you 15 milligrams of exosomes. So if you were curing them over 24 hours DR. ROSS CARTER: Yes. DOUG SPIEL: You're on mesenchymal stem cells. You would need a 150 million cells to make that many exosomes. DR. ROSS CARTER: So you're equivalent of that's extra 5 milliliter vial? DOUG SPIEL: So we our calibration is in terms of milligram. DR. ROSS CARTER: Oh, milligram. I'm sorry. DOUG SPIEL: So 15 milligrams. Now, we can proprietarily get 15 milligrams from about five to seven million cells, but the way we grow and expand and concentrate is a little bit different than the we run on the mills center. DR. ROSS CARTER: Let's say, you know, somebody wants like, lots of stem cells and they say, "I can't get that done legally here in United States" and they say, "Well I'll fly else to Riordan's Clinic in Panama, right. And go get tons of those cells," and I know people who do that. DOUG SPIEL: And there's some differences there, right? So if I get repeated doses, let's try intravenous doses. DR. ROSS CARTER: Yes. DOUG SPIEL: If I get repeated doses of a pool of umbilical cord stem cells that were expanded and you give me the same dose from the same pool, a couple of weeks later, I can have allergic reaction to that because now I have an adapted immune system that will have seen the antigens in those cells and cause an allergic reaction the second time. DR. ROSS CARTER: Is there still antigens on umbilical cells? DOUG SPIEL: Yes, they all have HLA type I. The MH II type IIs are not on this and that's why they use the term immune privilege. DR. ROSS CARTER: Right, which I've heard. But what about the HLA-DRs, is that different or the same? DOUG SPIEL: So I've been told by immunologists that the 1's are present, the 2's are not.
6 DR. ROSS CARTER: Got you. So there's still antigens. So when you expand those cells, it could cause reaction in your body? DOUG SPIEL: If you go out of the country, that's one of the risks. DR. ROSS CARTER: Would happen if you have that kind of reaction? What would you expect? DOUG SPIEL: We can have [indiscernible] including an anaphylactic life threatening reaction, specifically if you give it intravenously, so you get quite a severe cytokine storm. DR. ROSS CARTER: And so, the benefit of doing just the exosomes with that type of quantity of cells, you've removed the cells, so now you're just using the DOUG SPIEL: Just the exosomes. So, there's very, very tiny proteins and the only thing we've ever seen is mild allergic reactions which are really completely ameliorated by pre-treating with Benadryl. And I haven't even seen that with non-intravenous forms if it's true. DR. ROSS CARTER: If someone let's say a doctor is interested or who's been doing, let s say, regenerative procedures and have been using some of these umbilical cord products and things like that, they are like, "I really want to get better results but I know I can't do the things that I want to do that is illegal in this country." Is this would you say the next best thing or the next small thing? DOUG SPIEL: I think it's an excellent question. I think this is sufficient and as good as anything you could get out of the country, utilizing adult stem cells. D0R. DR. ROSS CARTER: And safer. DOUG SPIEL: Yeah, it's safer. And the real reason is, you know, we've all been kind of told by society that you need more cells, more cells. DOUG SPIEL: You don't need more cells. I mean I've treated people in their late 80s just with exosomes in their hips and their knees, some shoulders you know, those things get better. They get better because even though they're older and their stem cells are older, they are still present. And as long as the resident stem cells that are resident to the tissues, and I mean, all tissues. DOUG SPIEL: There's pre-cardio sites, there are pre-heart cells in your heart, in your liver, in your kidneys, certainly in your nervous system. So as long as those cells are still there, they are ready to be re-awakened. And just by infusing the exosomes into those areas, those cells will start turning like they were young again. DR. ROSS CARTER: Is there an age limit? DOUG SPIEL: I haven't seen one and I've treated up to 90. DR. ROSS CARTER: And the people that were that age still got positive results? And what conditions have you seen this work really well with?
7 DOUG SPIEL: Neurodegenerative diseases like the Alzheimer's, MS, strokes, common run-of-mill osteoarthritis or people who have bone-on-bone, you know. Are you aware why most of the people in this country go for total knees and total hips? DR. ROSS CARTER: Am I aware why? DOUG SPIEL: Yeah. DR. ROSS CARTER: Because doctors tell them to do it and they don t have an option. DOUG SPIEL: Well mostly because they have pain. DR. ROSS CARTER: Of course. DOUG SPIEL: So the larger argument with all of these patients is that some of them come in and they're always asking, "Will I grow a cartilage?" I always tell them as their age progresses, and the disease severity worsens, your chances of getting pain relief still remain high and your chances of your cartilage being reborn less-likely so and you may make less cells as you get older. But the real thing that you're trying to do deal with really advance population is take the pain away. Any growth that you get over and beyond that whether you use stem cells or exosomes or anything else, certainly is crazy. But, you know, you know as well as I know as an interventional physician and specifically as a pain doctor, you're here to make people's quality of life better. DR. ROSS CARTER: Exactly. DOUG SPIEL: And that really should be the yardstick. That should be the yardstick on whether you're doing neurodegenerative diseases, whether you're dealing neuropathic pain, whether you're doing peripheral neuropathy, whether you're doing any of these arthritis problems or ligamentous problems, it should always be quality of life, and that should be the yardstick by which you measure your patient's success. OUTRO: That's all the time we have. If you're looking for the best companies for stem cell products, exosomes, marketing, consulting or other products and services, please call us at 866-9WARRIOR for the best options. Mention this podcast for special pricing and offers. That s 866-9WARRIOR or Also, you can click the subscribe button below to be notified of all new episodes and please like and share this podcast with others. If you found value in this episode, please comment and review. That ll help this podcast grow. If you would like to learn more about this or any other speaker, click the link on our show notes or visit our website at regenerativewarrior.com. If you like to be a guest on our show, just go to our website and click the application link. You could contact me at drrosscarter@regenerativewarrior.com with show ideas or if you'd like me to present at your event. Until next time, this is Dr. Ross Carter signing off. [AUDIO ENDS]
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