Lecture: Stem Cell Therapy As An Antiaging Tool (Ozone Convention)

Hello. Hi, this is Dr. Joy Kong. I'm the president and founder of American Academy of Integrative Cell Therapy. I've been doing regenerative medicine for some time. I've been focusing on anti aging therapy and of course, using stem cells as a powerful tool for anti aging treatments. And to me, anti aging, the meaning of anti aging is to prevent decline. And so by preventing decline that we're really preventing disease. So that's probably the most powerful way to enhance health anyhow. So in my practice, I treat people with serious medical conditions, but I also help people who are already in great health, but they just want to use stem cell therapy as a tool to maintain their youth and vital vitality. So those are the two types of population. But anyone can benefit from anti aging therapy, right? We all want to maintain youth. We all want to function at the highest level possible. So to me, that's what anti aging is about. So I'm going to talk about stem cells as the tool, a powerful tool for anti aging treatments. So what I'm going to talk about, you know, of course we all know, we all want to function optimally and how do we achieve that and what is the cause of not being able to be at our best? And I think the root cause is the aging process. The aging process includes various causes, you know, has various causes. And. But that is eventually what's not allowing our body to repair itself and regenerate. And so one example is something as simple as osteoarthritis. People think, oh, that's a disease from aging, that when we, when we age, there's. They think it's wear and tear disease, that when you get older, of course, you worn on your body so much. But that's really, really kind of a naive way of looking at this. What's happening with osteoarthritis is that it's not a wear and tearing disease, it's a systemic inflammatory condition. Because when we were little kids, we wear and tear our body way more than how much we're tearing ourselves at 50 or 60 years of age. But our body can respond right away and get everything repaired. So one example is when you put an implanted. When you implant a knee construct, right, because you think it's wear and tear, then let's replace, let's put a new knee construct in the osteoarthritic knee, guess what? They get destroyed because. Because it's an environment that the inflammatory environment that's degrading the new knee construct. So it's not so much the Wear and tear. So it's really the regenerative capacity that's not keeping up with what's necessary for repair. And like I said, when we're little kids, we are running all over the place. We're doing all kinds of things that make our parents worry, but we get repaired right away and very completely. But what happens when we're older? You know, we're barely using our body very much and we're stiff, we can't get things repaired quickly. And then we suffer from long term, you know, these, you know, lack of flexibility, lack of strength and chronic pain. So really it's a, it's a supply and demand issue of how much are you able to be able to supply with what's necessary for repair and then what's causing aging? Right. So if aging is one of the causes that we can't achieve our optimal health, there are a lot of different hypothesis on what causes aging. And they all play a factor. So starting with mitochondrial dysfunction that we all talk about a lot about and genomic instability. So genetic changes as we age, you know, from, you know, the oxidative damages or from toxins that we bring into our body and there are epigenetic changes which are brought on by, you know, what we do with our lives and how that affect our genes and how our genes actually turn on or off. And then the telomere attrition. So we all know that as our cells divide, then we lose more and more of the length of the telomere and eventually the telomere length is not going to be enough to allow safe and accurate duplication of our DNA. And then also there's defective protein repair. So the, the, you know, if we don't have the correct protein, we can repair them. Of course, various functions in our body are so dependent on the proteins in our body then that our ability to repair will lag. And then also cells do go through a process of aging. So that's the cellular senescence. And what do all these cause? All these lead to eventually leads to impaired cell to cell functioning. And the bottom line is that if you can't have enough stem cells to replace the damaged tissue, then then you're not going to be able to fix whatever the problem move is. Right. So everything still leads to. The bottom line is if you can have all the damage you want, but if your stem cells are good, you can replace them then, then your body will have a new start. Right? But as we age, our stem cell also start to get exhausted and partially from all these factors and so the way I look at aging is it's like a house that's catching fire, right? So by the time smoke comes out, that's what I we've got symptoms. So that's when we can diagnose a person with particular condition. But what happens before the smoke comes out? You got fire was still going on, right? The smoke just doesn't all of a sudden come out in a split second. The fire has been smoldering in a house. So in our body, things are brewing. We just can't see it. The person looks okay because you're not noticing symptoms. It takes a lot of these fires to be catching on, collecting their momentum until more things are burned up and then you see the smoke. So the aging process is like the smoldering fire. And disease is when the smoke actually comes out. And this is why we have the phrase of inflammation. So inflammation and aging are so tightly connected that, that now we think them as kind of one entity. And so what happens when we age? We can check a person's inflammation by looking at their inflammatory markers. What's interesting is that even a person looks really healthy, right? Like this gentleman, you know, vibrant, you know, boxing, looking great. But his inflammatory markers are elevated, such as LA6 and TN Alpha. So the person has no, ostensibly no health issues, no infection, but these are elevated. But in young people you don't see such things because these healthy young person, these cytokines are very tightly regulated. Inflammation is actually the main driver of tissue damage associated with almost all age related diseases. So a lot of diseases come on more when we age, including cancer and different autoimmune issues or neurodegenerative issues and inflammatory response are pretty much associated with all of them. And these inflammation, the elevation of the inflammation markers actually can predict disease and disability in the aging population. And there's also evidence showing that increased inflammatory markers are strongly linked to poor physical performance, decreased muscle strength, cognitive decline, and also early death. Stem cells has been shown to be a tool, an anti aging tool, by targeting inflammation. For example, in a ratio traumatic brain model, the intravenous infusion of msc. So mesenchymal stem cells actually can decrease brain inflammatory cell infiltration, the microglial aggregation and apoptotic cell numbers, so reducing the damage, reducing cell death. And in another study, they looked at 172 patients with RA and 16 with lupus, and they transplanted allogeneic, which means from another person. So allergenic MSCs actually helped reestablish the immune balance, shifting the immune system from a Pro inflammatory inflammatory to an anti inflammatory state. And there's significant decrease in IL6, TNF alpha and CRP levels. And then another study, patients with ankylosing spondylitis with high disease activity, when they infused these allergenic from another person, mscs, that also decreased the inflammatory marker and decreased disease activity. And they also have shown benefits in Crohn's disease that the MSCs not only have improved these people's quality of life, but they, the CRP levels was also improved. And so the thought is if we can slow our decline and slow the aging process, maybe we can repair faster and better and then we can slow the aging process. Right. So stem cells is a very, very hopeful way of achieving this. And I'm going to show you some of the the stats. So you know, we all know that we all came from a single stem cell. So the fertilized egg, that's the, you know, where the miracle starts. And that eventually make an incredible human being like us, you know, thinking, talking, accomplishing things and enjoying life. So what can we do to harness the kind of intelligence that actually allows the formation of life? If we can tap into that kind of intelligence, that would be remarkable. Right? So we, we all knew stem cells is incredibly powerful, but does it actually work in real clinical practice? So that was the question when I first got into the field. You know, of course I heard about how great stem cells can be and they sound, you know, amazing, but does it really work? And it's only when I started seeing patients getting incredible results, not just my own patients, but, you know, patients treated by other doctors. The kind of results are pretty irrefutable and incredibly inspiring. So one thing that we have to accept is that as we age, we're losing our stem cells to a very, in a very rapid pace. So that's just a fact of life that we have to accept when we were first born. This is a ratio of the number of mesenchymal stem cells in your body versus the number of total cells, total number of cells. So, so when we're born, every 1 in 10,000 cells in our body is a stem cell is MSC. So MSC is really considered master regeneration. And they're all over our body, everywhere. Where your tissue is vascularized, MSCs are there. So 1 in 10,000 when we're first born. And then when we grow to teenage years, it has lowered to 1 in 100,000. So that's tenfold decrease as far as the ratio. And then when we reach our 40s, it becomes 1 in 400,000. And when we reach our 80s is 1 in 2 million. So you can see this is the graph of that drastic decline. It's like we're running out of these stem cells, out of these powerful cells that can help our body to regenerate. And I talked about msc. So before they get into the blood vessels, they're called parasites. So they're peri. So they're wrapping around blood vessels. So in every tissue where you have blood vessels that's supplying the nutrients and taking away the waste, these cells are there. So what they do is that not only there, you can, you can look at all those, you know, tentacles, right? All these, you know, these extensions of the cell where they actually are not only trying to sense what's going on in the blood, they're trying to sense the signals, but they're also communicating with the neighboring cells. So they kind of help have their pulse on the whole neighborhood and the environment and monitoring what's going on, what's flowing through your blood. So you're systemically what the signals are. They can also detect. And these are what they look like under microscope. And they have been proposed to be renamed medicinal signaling cells by the doctor, Dr. Kaplan, Arnold Kaplan, who discovered these cells. And so now he wants to rename these cells as medicinal signaling cells because he thinks it's a kind of a misnomer to call them stem cells because their main function is to produce signals and these signals will promote regeneration. So the MSC's mesenchymal stem cells or medicinal signaling cells have a lot of different properties. I want to go through them really quickly and a lot of audience I'm sure already know, but it's really pretty exciting. You know, maybe a couple of them, you don't know, for example the anti inflammatory effects. So they secrete a lot of anti inflammatory molecules that can calm inflammation. Of course, you know, when you're acutely inflamed, you really can't quite regenerate and repair. Even though the acute inflammation is an important process in healing. And then the immunomodulatory effect, that's what we saw in the immune modulation where you can shift immune system from a pro inflammatory to an anti inflammatory state. And the regenerative potential, you know, that's mostly through the paracrine effect, which just means secreting signals in the neighbor in a small neighborhood instead of endocrine which is secreting your signals into the bloodstream, affecting the whole body. So the paracrine effect includes sending out all these growth factors to neighborhood other cytokines and they also communicate directly with local stem cells. So the kind of regenerative actions they, they, they trigger a lot of times is by talking with the local stem cells, not by themselves becoming a new cell. Let's say, you know, cells is put in the, in a muscle, right? The muscle cells may regenerate, but, but guess what it came from? It came from the local stem cells that actually are destined to regenerate to differentiate into muscle cells. Not so much of these MSCs that's injected, you know, very, very tiny amount of them may differentiate. But there's been decades of research. Now we realize that even though we were hoping that these cells will differentiate into everything. But what we found out is that the, the vast majority of this is effect maybe over 95% of how it works is through these, these paracrine effect by sending out signals to neighboring cells and allowing the local stem cells to actually do the real cell differentiation and replacing the damaged cells. And mitochondria transfer angiogenic potentials. It's really important, right? Without blood supply then the tissue is not going to survive. And so in various tissues they found these incredible androgenic potential from these stem cells. And mitochondria transfer is another very interesting mechanism where these implanted cells, especially if you implant young healthy cells, they will have young healthy mitochondria. So these mitochondria has been shown under electron microscopy to be transferred into the recipient cells. So actually revitalizing and energizing the cells in the recipient. Right. And then anti fibrotic properties has been shown over and over again for various. Either local fibrosis, even like Peyronie's disease has been shown in lung fibrosis, liver cirrhosis. So it's very powerful in breaking down scar tissue. And anti apoptotic. So when, when cells are, let's say you have stroke and there's an area of decreased blood flow and some cells will die because they are starved of nutrients, but the neighboring cells will end up receiving these signals from the dying cells and they may go on these apoptosis. Right. We know that the infarct size, it's often a lot bigger, larger than where the blood supply is lost. So that's the apoptotic process. And what stem cells can do is rescue these cells that are, you know, otherwise are going to go on a program cell death either because of chemical or, you know, or vascular injuries and radiation injuries. So can actually rescue them. And the reverse, the pro apoptotic is also very important because will have seen these cells when they look at, when they get in contact, especially younger cells, when they get in contact with pre cancerous or cancer cells, they will have these surface markers or, you know, characteristics that these cells can recognize that these are pathological cells. And then they can send in particular factors, including what's called, like a trail, what's called trail ligand. So that actually can get into these cancer cells and trigger apoptosis, so make them die. So that's incredibly powerful too, as well. And then antimicrobial. We know that these MSCs actually secrete antimicrobial peptides. So they have been shown to be beneficial to fight bacterial, viral, fungal, and protozoan infections. And I want to talk just a little bit about young versus old MSCs. So what do I mean by old? Of course, the older you are, the older the MSCs are. But, you know, even a person's 20 years old, I still think that's an old MSC. If I'm getting cells from this 20 year old, that's still way older than something from, from the umbilical cord or placenta. Right. Of a newborn. So day zero versus day, not day, year 20, that's. There's a huge difference. Or even when a child is 6, 7 years old, their cells would not nearly be as powerful as what's in the birth tissue. So I want to show you, you know, talk about whether or not age matters, because this is an important thing, because if the, you know, initially stem cell therapy was done, the first stem cell therapy was bone marrow transplant. So bone marrow were the earliest source of stem cells. And then later on we realized, oh, there are stem cells in other tissues too, not just the bone marrow, because some, you know, a few decades ago, we still thought that only bone marrow has stem cells. So there's, there's an evolution of where we think we can find these stem cells. And, and then later on they found stem cells in fat, and then they realize it's everywhere. So. But when these stem cells are basically staying with you your entire life, right, you're born with a lot of stem cells. So what happens when you carry these stem cells with you everywhere? You know, every job you've had, every party you've had, every country you've traveled to, you know, every bad food you put in your body, they're there with you. So there is a lifelong accumulation of things that can damage you. And these damages will actually make the cells more prone to cell death. They will lead to cell senescence. And these damages can result in loss of regenerative functions and even neoplastic transformations. So the cancers changes. So that is, you know, you know that that's what we need to keep in mind. Just because we have stem cells, they are our cells, they've been with us all this time. But when you Compare with neonatal MSCs, so that includes you know, cells from the umbilical cord, you know, umbilical cord tissue, cord blood, placenta, there are very, very few cells in amniotic, amniotic fluid, extremely few cells. But all these are neonatal and these are spared of the pro aging factors that we have in the stem cells in our body. I want to show you some evidence that age does matter. So this is not just my opinion. These are from people who have devoted many, many years to understand the differences. So one study that looked at adipose derived msc, so this is from adult person, which means that it's an aged MSc. So what they found out was that they are significantly compromised in their ability to support forming a new vascular network. And then when there's wound in the skin that these cells were not able to rescue, you know, these healing, basically they're not able to rescue age related impairment in the healing. So because they're old themselves, so they can't make the healing any better. And then another study in 2014, they looked at bone marrow derived MSCs and they have less myogenic potential and less engraftment properties when they're compared with developmentally early MScs. Then another study looked at bone marrow derived stem cells and they exhibit age related decline in inflammatory response in cytokine chemokine receptor expression that are important for migration of these MSCs and their activation as well as their immunomodulatory activities that's so important for their function. So they do decline over time. And then genes that are related senescence start to increase in these adult stem cells. So this one, the first study you know, that shows shows in adipose derived MSCs and then aging can also affect the availability of certain type of stem cells that are important for their angiogenic potentials. So you're losing certain cell types. And then as we age they've shown in bone marrow derived stem cells there's increased level of reactive oxygen species. These cells will start to accumulate higher levels of these reactive oxygen species. And not only they have higher levels when these cells, because they're older, they're also more sensitive to the reactive oxygen species. And that further impairs their ability to, to be therapeutic, to be helpful. And when we looked at so in a 2010 study, they looked at young MSCs, which is from somebody age 1 to 5 years of age, they outperformed older MSCs, and that's from somebody 50 to 70 years of age. When they looked at how well these cells are able to help people recover from MI right after heart attack to see how well their cardiac function can improve. So the young stem cells definitely outperform the older stem cells. And then MSCs from young individuals can also have a broader potential for differentiation, such as developing into neuroectodermal type of cells. So they can do that in vitro. But when you looked at bone marrow derived stem cells from elderly patients, they can't do that anymore. So they lost certain potentials. And also you have to realize that we have been exposed not to only toxins, but to drugs. Right? We have a lifetime to accumulate different things and something as benign as NSAIDs that so many people take liberally and that may inhibit MSC's ability to differentiate into, into cartilage. Also it disrupt their ability to help bone bone formation. So so these medications are, are, can damage our stem cells and also lifestyles, something like our diet. So this study, 2013 study looked at adipose direct stem cells from mice that's been fed high fat diet. And these mice, you know, these MSCs turned out to tend to form fat cells. So they tend to differentiate preferably to fat cells instead of endothelial cells. So it changes how they differentiate. So these are lifestyle, you know, your diet and even in obese patients. So they looked at how well the stem cells in an obese patient are able to differentiate and they realize, oh, they have less ability, impaired ability to form new bones. So when they looked at the new bone formation, the mineralization nodules are fewer and they're smaller. And metabolic diseases like diabetes also also change the adipose derived stem cells change their environment and diminish their ability to establish vascular network both in in vivo and in vitro. So and we know how prevalent obesity is and, and how, you know, more than a third of the population is overweight and more than 8% with diabetes. So this is not an insignificant issue. When we agent mesenchymal stem cell, they do age. And this is one article that talked about how aging can lead to decreased bone marrow MSC pool. So reduced number of MSCs and then a biased differentiation. So they prefer the cells will tend to differentiate into adipocyte and at the cost of osteoblast. So they have turned more into gone the path to form fat rather than form new bones. And that is one underlying etiology for osteoporosis we all know as the bone marrow age. The bone marrow start to take on a different color. Instead of red, they look more and more yellow, so it gets more and more fatty. And then when we transplant young MSCs into the bone marrow of aged mice, not only it can rescue bone loss, but it can also delay aging. So when you transplant, it help their bone growth reduce bone loss, but delays their aging. And what's really fascinating is that even if you put these cells subcutaneously, it can still suppress age related degeneration of various organs. So that's the systemic effect of these cells that they're able to first can get into your bloodstream. But even local cells, they can secrete these factors that will get into your systemic circulation, so they can provide these anti aging benefits. And so the aging of mscs, not only is it detrimental to the skeletal system, but also to non skeletal tissues, including the hematopoietic system and aging. So aging does compromise the therapeutic potential MSCs. So these, the aging I'm talking about is not just from the cells from aging individual, but also cells that are cultured for many passages. And this is one reason that I'm, you know, I'm very careful about when people want to use growth cells and culture for, for many generations and so they can achieve huge number of cells and that can lead to cell aging and besides all kinds of other issues. So the transplantation of MSCs from young donors can actually delay aging in mice. Stem cells from older donors do have defective function, such as impaired capacity to proliferate and differentiate when they compare to young cells, cells from young individuals. And when you looked at, when you look at bone marrow derived stem cells isolated from either young or old mice, so young is 1 to 2 months old, old is 20 to 24 months old. The bone marrow MSCs from older animals had significantly less capacity for differentiation into bone, muscle, fat or neurons. Also any of these differentiates, all their differentiation potentials have lowered. But when you transplant young bone marrow derived stem cells, that can significantly delay the decrease of bone density. So it delays the osteoporotic parotic process. But you know what's scary is if you transplant old bone marrow derived stem cells that can accelerate the decline of bone density. So you're actually causing some harm. And so what can stem cells do about aging? What are some of the evidence? I want to show you a little bit. So this is a study that I'm going to talk for quite a few slides. They're looking at the properties of either human amniotic membrane derived or adipose derived stem cells. You know, to look at how they can extend lifespan in this these rats, these fairly common rats. So aging does lead to progressive deterioration of the cholinergic and dopaminergic system. The concentration of these neurotropins in both the brain and muscles decline and that lead to reduced neurogenesis and accelerated muscular atrophy and that can impair neurotransmitters both our cognitive function and our physical function. Aging can lead to exhaustion of our stem cell population. As we saw earlier on various stem cells can exert neuroprotective effects and enhance functional recovery by secreting these neurotropic factors. There's concentration of these toxic substance like the T bar byproducts. Lipid peroxidation also significantly increase in the brain, muscle, heart, liver, lungs of aging rats. Lowered blood vessel density. That's what happens when we age. When they transplanted adipose derived mscs into this Alzheimer model mice, they showed increased brain concentration of acetylcholine, BDNF and ngf. And with improved cognitive and physical function of these aging mice. And adipose derived MSCs also can secrete a high concentration of VEGF vascular endocrine growth factor and that can contribute to the prolongation of lifespan in an ALS mouse model. And even muscle derived stem cells can help extend health span and lifespan of a progeria mice model by restoring these microvessels and muscle fibers by the, you know, these factors that they secrete. And in. In their experiment they looked at aged mice so 10 months old aged mice and they were divided into three groups with control with a group receiving amniotic membrane derived MSEs, another group receiving adipose derived MSCs. And they used young rats, seven seven week old rats as control healthy control. So they did intravenous infusion through tail vein of the amniotic and Adipose derived MSCs and they were given to these rats once a month until they die. So amniotic membrane and adipose MSCs have been shown to significant to improve cognitive and physical function of these aging rats and extending their lifespan by 23 and 31% respectively. So these two groups show slightly different, but they both extended lifespan and by the time the rats reached 20 months of age, only 30% of the controls are still living. But 70% of the amniotic membrane derived stem cell group and 100% of the adipose MSC derived group treated group actually are still Alive. And by 23 months of age, all the rats in the control group have died. But in the treated group, the survival rate is 60 to 72%. So that's pretty remarkable. And the transplanted cells were also found to differentiate into neurons. And the differentiation rate is between 54 to 76%. So that's also very interesting that they, that is, you know, even though majority of their function is not to differentiate, but here we've seen, you know, quite a significant differentiation. And when they looked at these various brain neurotropic factors, they've shown that they were all upregulated in the treated group. And VEGF also that possessed the angiogenic potential was greatly increased the levels even higher than in younger rats. So the treated older rats have higher level than the younger rats. And when you looked at the muscular neurotropic factors, they were also restored. And some of them were restored and upregulated and improved the motor neuron development, muscular innervation and to the level higher than in younger rats. And the transplantation of both groups actually significantly improved the number of vessels comparing to, you know, comparable to the younger rats. So basically you are kind of bringing them back into the younger state. And tissue injury was nearly fully attenuated by the transplantation of these MSCs. And the monthly transplantation of the MSCs markedly increased the stamina and the cognitive function of these old rats. The acetylcholine concentration in CSF M mussels were also restored. So, you know, they were declined significantly as they've aged, but they were also restored. And the alteration in the gene expression of the cholinergic nerve markers associated with aging were also restored. So one mechanism, I didn't even talk about that in how MSCs work, one is that when they secrete exosomes, containing exosomes are micrornas. And these micrornas can cross the cell membrane, the nucleus, the nuclear membrane, and actually interact with the DNA and help repair some of the DNA damages and change methylation patterns. So that's things happening on the genetic level. And the number of host stem cells in these age rats, even though they were very low, right, you know, less than 30% that of young rats, the transplantation actually increased the number to the level that's comparable to the young rats. And then the expression of certain chemokines that suppress neurogenesis, that's associated with aging, and also markers associated with neural skeletal proteins, these were also reversed. So these unfortunate changes that associated with aging were reversed after we gave the rats received stem cells. So basically, in short, the transplant stem Cell transplantation increased the concentration of acetylcholine and various neurotropic factors and that restored the cholinergic and dopaminergic nervous systems, improved micro vessels and muscle mass, and then antioxidative capacities. Here's a different study that's also very interesting. They were looking at bone marrow transplantation from young mice to old mice. They were using mice that are pretty old, 15 months old, which is equivalent to human age of 75 years, where 50% of their peers have died. At this point, they were giving intravenous bone marrow derived MSCs to these mice and the dose were 100 million of these nuclear cells. Not just MSCs, but there are some MSCs in there, small percentage. But the nucleated cells are also incredibly helpful. So they were injecting them through again intravenously and they repeated it six times within three months. They used mice that were very young, aged three to 15 months, as the donor. The results is that the maximum lifespan in the transplanted mice were increased by by over 30%. And the survival time from the beginning of the experiment to the time where of course, survival time starting from the beginning increased by 3.2 fold. Which means that the rats that got the stem cell transplantation from the time of the start of the experiment had three times as long to live as the control group. And at age 19.3 months, the last mouse of the control group actually looked kind of sad. They died sedentary, almost immobile and with a hunched back and poor hair. But the group that had received the transplant actually were active. They had even spine and shiny even hair. The observed lifespan extension was accompanied by extension of health span. So they're more active and they're healthier. And there's also chimerism. So the integration of the DNA six months after transplantation, that was about 28%. So that's a very encouraging result looking at our aging population. So this is another study looking at humans and what stem cell transplantation can do for chronic inflammation and aging. So all these patients had some kind of inflammatory condition such as osteoarthritis, post traumatic arthritis, inflammatory back pain, shoulder bursitis or herniated disc. They give one time IV infusion of 25 million umbilical cord blood derived stem cells and there's no side effect noted. And 10 patients show significant improvement in the lab tests and anti aging benefits. So the inflammatory markers in three months did not show change, but they have shown improvements. Half the patients showed improvements in these basic labs. And then when they looked at different parameters like skin, hair, nail growth, energy levels, libido, mood, sleep and pain level, those have all been improved and significantly. And you know, lastly, I want to talk just a little bit about frailty. You know, as people get older, people get frail and that can be manifested by, you know, decline in limb, body mass, strength, endurance, balance, gait speed, activity level, energy level and also organ reserve. So the frailty is a big issue. Increase the risk of falls, hospitalization, institutionalization, disability and death. You can measure frailty using this CHA index. So there are five criteria. Weak grip strength, low energy level, self reported exhaustion, slow gait speed, low physical level and or unintentional weight loss. So the prevalence of frailty, which means you meet at least three out of the five criteria. So the population with frailty in our age over 65 group is 7 to 12%. So approximately about 10% of these, you know, people over age 55 are, do have frailty. But there's also pre frailty where they meet one to two criteria out of the five. And that prevalence in the same population is about 35 to 50%. So that is a huge population. And the comorbidities are actually much are much more prevalent in the pre frail population compared to the non frail population. So there's various declines in cardiovascular, pulmonary, musculoskeletal, neurologic and psychiatric conditions. So there's significant decline even if you just pre frail. And there's strong link between frailty, inflammation and impaired ability to repair tissue because of decrease in, in the stem cell population and stem cell activity. And so we all know our own stem cell population and function decline with age and aging can actually induce what's called quiescence to senescence switch. So these cells, you know, they instead of just being quiescent, they become senescent. So they actually degrade. And that can also cause degradation in the extracellular matrix and impair the niche that they're in. And that can reduce the stem cell ability to renew themselves to maintain their vitality and their regenerative potentials. So then these have been linked to the frailty syndrome. And MSCs also undergo senescence. And so we talked about that, you know, various properties impaired. And then when they deliver allogenic MSCs, they've shown that not only they're safe, but they can produce significant improvement in the physical performance and measures and inflammatory biomarkers. So there's significant improvement. So what I want to talk about next is that. Okay, that all sounds great. So what does that mean for my practice? What can I do? So I want to talk about the protocol a little bit. And before I talk about protocol, I want to mention it's almost impossible to do an anti aging regimen using a person's own stem cells. First of all, the moment you take your stem cell out, you have just decreased your own stem cell supply. So you can take them out and use it for particular condition. It can help. But you have reduced your own stem cell supplies. So that's no question. But also when you go through surgical procedure, when you either drill into somebody's bone or you do a liposuction, you get the fat out. You just created an injury, you know, not a small injury. So you created an injury. And when these cells are put in the body, guess what the cells are attracted to? They're attracted to inflammation and injury. That's how they work, that's why they're there. They are sensing what's going on, what kind of signals are sent through the blood. And then they will respond to that signal by getting into your blood vessels and swim upstream, finding those signals and getting out of the bloodstream and exert local effect. So you can imagine if you just produce an injury and you give somebody these stem cells, some of those stem cells are going to go right into the areas that are screaming, help me right to, to start the repair process. So that, that's something you need to think about. But also these cells from our own body, like I mentioned, it has aged. There's no way around it. It has been with us for all these years, it has aged with us. So it's not as good. Not only is it not as good, there's also more of a potential to do harm. You know, we've seen that, you know, infusing older MSCs can also can potentially lead to acceleration of the bone decline. But we have also shown, we have seen evidence that our own MSCs, for example, adipose rev MSCs, when they put it next to cancer cells, in that instance, they used a glioblastoma multiforme cancer cells. From both in vivo and in vitro experimentation. The adipose derived mscs cause the cancer to grow, to flourish. But the umbilical cord MSCs actually, you know, make them reduce in number and size and getting rid of them. So there's huge difference. And also it's impossible to do an anti aging protocol using a person's own, you know, cells. Not only you are doing a liposuction or you know, bone drilling periodically, but also, you know, you, you know, you just can't sustain that on a Regular basis if you're trying to do anti aging practice and if you want to extend or expand the cell population to a huge number. The problem is that the more you expand, the less potent the cells are. When you expand cells upon certain populations about four generations, they're going to start to decline. And even before that, a lot of times if it's not the perfect condition, they will not go. You know, one stem cells are not going to divide into two identical stem cells. They often divide into one stem cell and one daughter cell. So it's very difficult to control. And so you end up with a big population. But a lot of them are not the original stem cells anymore. More so. These are some of the reasons, this is why I'm a big proponent of birth tissue derived stem cells and mostly umbilical cord stem cells because these are so young, so potent and they are also safer as far as preventing the, you know, triggering the growth of cancer. So various reasons, but also of course they're very convenient and you can do it on regular basis. I have been doing stem cells on myself. I do IV infusions on myself. It's been five years, I've been doing it every three months. So that's my protocol. But I'll show you the protocol and how to calculate the dosage. What you want to do is minimally manipulated birth tissue derived MSCs. So those are the benchmarks. These are the master regeneration. Not that other cells are not helpful, but you need MSCs. So with these MSCs, you know, I do not, you know, in the US you, you, unless you have a, you know, you're under ind, you can't manipulate the cells which include using enzyme to obtain the cells or altering the cells with any kind of chemicals or expanding, growing them in large numbers. But you can use minimally manipulated cells and they are considered tissue transplant. So that's what I would advise providers to use. And the MSC dose would be 2 million MSCs for every 60 pounds of body weight. These are non expanded, right? Unexpanded stem cells. Most of the studies when people look at high numbers, those are expanded stem cells. So a lot of dosage are really high. They will give you some recommendation. The range has been between 0.2 to 1 or even 2 million cells per kilo. So that's a huge number, huge number of cells. But if you're using minimally manipulated cells, the cells are going to make more of themselves in the body. Right? I think the human body is the most ideal incubator will be way more sophisticated than the incubator that's sitting in the lab. And also our body will give the cell certain signals. So the cells will respond to what's needed and a direction of how they should differentiate and how they should, what kind of exosomes they should secrete. So it's a targeted response. And so when I calculate the dosage, 2 million cells. So 2 million cells, you know, I'm talking about 1cc, you know, 1cc has 2 million cells. I'm talking about, you know, the product that actually has that high of a dosage. So you add another 2 million for if somebody has age over 65 to 70 and you add another 2 million for somebody that has really severe or disease condition. So that's a pretty simple dosing kind of regimen. And as far as the treatment, how you should do it, how frequent, if somebody comes to me initially with any kind of health issue, I will give them, treat them at the recommended dosage. The average dose will be between 2 million to 8 million. Right. So 2 to 4 ccs of 2 million per cc product. So once I give them the treatment, then I want to see how they do. I'm not a very dogmatic person. I don't say you have to do how many numbers within how long, because I've seen people who recover incredibly with just one treatment. And there are people who need a series of few. So I'll tell them, let's wait for four to six weeks, depending on what you're treating. Neurological conditions sometimes takes longer because it takes so long to observe any effect, any changes. But on average between four to six weeks we can do a booster. If you need another booster, we can do that as well. So that's the initial treatment phase. Get a person to a really good state and then you enter the maintenance phase. And that's, you know, in general, I tell people, yes, you know, probably once every six months because the cells usually stay in the human body for about three months and then their effect will last for about another three months because they do secrete these factors and they do have downstream effects. And also the MRNA's from the exosomes will get into cell nucleus that can produce, you know, longer term benefits. The intervals can range between 3 to 12 months. And I have patients who want to do, you know, every two months or even every month. But, but it does get, get very costly. So most of my patients are doing, you know, between three, you know, between three to to 12 months. Most of them, you know, between three to six months. So that will be a good anti aging regimen. So we have a lot longer lifespan comparing to mice. And the mice we're getting once a month, so we don't need to get as frequently. I believe every three to six months is a really, really good interval. And of course the patient can always, you know, be very, be more aggressive about their own anti aging regimen. And so I think through these powerful, powerful methods, we can really help our patients to live more years and with more vitality, you know, in these remaining years. Because there's, you know, years don't mean anything if it's not healthy and it's not, you know, enjoyable. So that's the end of my talk. If you want to reach, reach me. That's my email. Joykongmdmail.com so I don't know if there's any questions, but that's the end of my talk. Okay, so I don't see any questions yet. Then you know, if you have any questions, that's, there's my email. Feel free to contact me. I, you know, one of my missions is to help doctors to really have a good understanding of stem cell therapy and not only of just the general idea, but also exact protocol how to do this and also what kind of evidence out there. So there's actually a online training course, it's called Fundamentals of Stem cell practice on American, on the academy website. So it's just aict.org so if you want to go on aict.org you know, under training, there's that training course and, and, and you can, you know, receive a certificate at the end of the training. It's extremely helpful. It's very practice oriented. So I hope I see more of you there.