Stem Cell Therapy as An Anti Aging Tool

Next up, all the way from Los Angeles, California, triple board certified, Dr. Joy Kong. She's going to talk to us about anti aging and stem cells, something that we're all pretty excited about. So happy to have you here, Dr. Kong.

Thank you.

Sean agreed to go forward.

Okay. Hi. So I think of anti aging as something that's really exciting and I do that a lot in my practice. So, you know, aging. And I'll talk about why anti aging is so important. That's really, I think, the number one thing as physicians that we should do, which is to prevent any diseases from coming up in the first place. So. So first of all, we all seek to have the optimum. We all want to function at our highest levels. But what is preventing our decline of what's resulting in our decline, which is really the aging process. And osteoarthritis is a good, you know, illustration. We tend to think that, you know, we tell patients it's wear and tear disease and it's really not aware. And tear disease, it's a systemic inflammatory condition. And that can be illustrated by implanted knee construct. If you put in the osteoarthritic knee, those construct will be destroyed. So it's really the lagging regenerative capacity that's the problem. That's the basic, the foundational cause of osteoarthritis. And you know, talking about wear and tear, we have all, you know, gone through plenty of wear and tear when we were little kids. You know, I wore and tore myself a lot more when I was 10 years old than now. But the repair is rapid and complete. But what's happening at an older age? So it's the repair is the supply that's not keeping up with the demand of the damage. So what causes aging? There are a lot of hypotheses and there are many different aspects that people have looked at, including mitochondrial dysfunction, genomic instability, there's telomere issues, there's epigenetic changes and protein repair problems, cellular senescence. But in what it all funnels to is inflammation, which we know is the fundamental cause of aging and disease. And that has to do with stem cell exhaustion in the end, because whatever damage you cause, you can't replace the damage. If you can't regenerate replacement tissues, then basically you are degenerating. And what is disease and what's aging?

And.

And the analogy I have is a house that's catching fire. So if you look at a house, when a smoke comes out, that is the symptom of disease. So now we know, okay, so the house is on fire, but what's happening before the house is on fire? There's smoldering fire that's going on in the house. Right. Just because you can't see it doesn't mean it's not happening. And that's the aging process. And, and that's why we have the phrase inflammaging. So inflammation and aging is very closely linked. And what are the markers of aging? So this is a very healthy looking elderly, you know, older gentleman. But even in apparently healthy elderlies, the level of inflammatory markers such as LS6 and TN Alpha are elevated. And in the absence of any infections. But these markers are tightly regulated in younger people. And inflammatory response is the main driver of damage associated with almost all age related diseases. And these levels can predict disease, not only disease presence and also disability. And these markers are strongly linked to poor physical performance, decreased muscle strength, cognitive decline and early death. And so here is an article about stem cells used to target inflammation. And they did a, there's a study, IV infusion of MSCs into a rat that has traumatic brain injuries or TBI model and it showed decreased brain inflammation, decreased microglia and decreased apoptotic cell numbers. And in another study where they had rheumatoid arthritis patients and lupus patients and that showed allogeneic MSCs helped to re establish balance in immune system. So from a pro inflammatory state to an anti inflammatory state. And in patients with ankylizing spondylitis with high disease activity, these allogeneic MSCs also decrease CRP levels and decrease disease activity. And in Crohn's disease the biological markers showed improvement and then also improved quality of life. So these are some correlations between inflammation, decreasing inflammation and improving in the person's condition and improving these inflammatory markers. And so if we slow down the disease process, can we slow down the decline so that we can repair faster and better? And this is what stem cells can come in as a powerful anti aging tool. So we all know we're made from stem cells. I don't have to tell this audience coming from one single cell. And now all of you sitting in front of me, these miraculous human beings doing incredible things in the world. So how can we harness these cells? But undeniable fact is that as we age, the number of cells just start to drop off. So when we're born, one out of 10,000 cells in our body is an MSC. When it comes to teenage years becomes one in 100,000 when we're in our 40s, one in 400,000. And when it comes to our 80s, it drops to one in 2 million. So this is a graph of the sharp decline of our stem cell supply. So what are MSCs? We all know their parasites before they got into the blood vessels and, and they have been shown to have such pivotal role in orchestrating regeneration that Arnold Kaplan wanted to rename them medicinal signaling cells. And how do they help us? So they have a lot of interesting properties. You all know about this anti inflammatory immunomodulatory regenerative potentials triggering local stem cells, angiogenic potentials, they can have breakdown scar tissues. There's anti apoptotic properties when the cells shouldn't die, they salvage them. And then pro apoptotic properties when there are cells that should die, such as senescent cells and cancer cells. And then antimicrobial properties that we have seen that they actually secrete antimicrobial peptides and then also something called mitochondria transfer. That's really exciting that they've caught on electron microscopy that stem cells can actually transfer their mitochondria into macrophages and energizing the macrophage. So there's something I want to talk about which is young versus old MSc. So does age matter? This is a big question. Are all stem cells created equal? So the fact that these MSCs are persisting in our body in our whole lifetime really predisposed them to carrying out or absorbing all the damages that we have done to them. So the, you know, the accumulation of the cellular damage can lead to cell death, senescence and loss of their functions and even neoplastic transformation. But neonatal stem cells don't have these issues. And so I want to show some evidence that age does matter. For example, aged adipose derived MSCs are significantly compromised in their ability to support vascular network formation so they're unable to rescue age associated impairment in cutaneous wound healing. And another study showed bone marrow derived MSCs have less myogenic potential and engraftment properties than developmentally early MSCs. Another study showed bone marrow MSCs exhibit age related decline in inflammatory response cytokine and receptor expression that's important for these MSE migration activation. Thus their immune modulatory activities. And some more evidence gene related to senescence also start to accumulate as adipose derived stem cells, you know, age as they, you know, age with us. And aging also alters the availability of these particular stem cells that are important in angiogenesis. So actually start to reduce their availability and their capabilities and there's also increased level of reactive oxygen species in aging bone marrow stem cells. So not only they have decreased level of reactive oxygen species, but older adipose red stem cells are more sensitive to microenvironmental reactive oxygen species. It's a double whammy. They have more roc ros and then they also are more sensitive to them. So that further impaired their therapeutic potential. A little bit more evidence. Young MSCs, which, from a person age 1 to 5 years of age, outperformed older MSCs from someone 50 to 70 years of age in improving cardiac parameters after MI. Here's another study. MSEs from young individuals can undergo neural ectodermal differentiation in vitro. But bone marrow MSCs from elderly patients have lost that capability. And adult MSCs are also exposed to a lifetime of factors that we've done a lot of things to ourselves, including something as benign as NSAIDs. And NSAIDs can inhibit MSC's chondrogenic potential and disrupt bone formation. So these have real consequences. What we do, what we put in our body. Lifestyle factors do affect the qualities of our MSCs. For example, they showed that when mice are fed a high fat diet that their, their MSCs have a more potential to become adipocytes, to become adipose cells rather than endothelial cells. So it changes their differentiation pathway. And also in obese patients, the ability of these cells to form bones are also impaired. They've shown that mineralization modules are fewer and smaller. So when something, you know, a lot of our patients actually have diabetes, right? So diabetes can also alter the cell environment, and that also impairs the cells, the MSC's ability to establish vascular network. They've shown that both in vivo and in vitro. And so we all know that, you know, sorry about the cutoff, but, but adults at age over 20 are, you know, about 35% are overweight and 11% are obese, and 8% have diabetes. So this is a, you know, this is not an insignificant problem because this, you know, this kind of impairment can happen with such a high proportion of our patients. So this is a study that's looking at mesenchymal stem cell aging. So aging can lead to decreased bone marrow MSC pool. So reduced number also affect their differentiation pathway into more of the dipocyte at the cost of osteoblast. So instead of helping with bone formation, they become fat. And when you transplant young MSCs into the bone marrow of aged mice, not only can rescue the bone loss, but it can also delay aging. And what's really cool is that even subcutaneous implantation of these young MSCs have a beneficial effect in preventing aging of various organs. And aging of MSCs can also be detrimental to non skeletal systems, including the hematopoietic system. And aging also compromises therapeutic potential of MSCs, including cells not only from aged individuals, but also when cells are cultured for many passages. So you know, this is another reason that I'm very cautious about cell expansion or people who, you know, who are generously giving these expanded cells. I think there's something to be cautioned about another Study about transplantation MSCs from young donors that can actually delay aging in mice. Stem cells isolated from older donors tend to have defective functions. And when you compare functions of bone marrow MSCs isolated from young mice versus old mice, so 1 to 2 months to over 20 months, old bone marrow from older animals have significantly less capacity for differentiation. When, when you transplant young bone marrow MSCs that significantly delays the decrease in bone density. Right? So it reduces this bone degeneration. But older bone marrow derived MSCs, when you transplant those, it may actually accelerate the decline in bone density. So that's something that has not been talked about. We think that as long as you put stem cells in the body, it's going to be good for you. But what if you put defective stem cells that actually going to accelerate your decline? And what can stem cells do about aging? This is one study that is talking about. It's really nice study that shows many, many aspects but it's looking at cholinergic and dopaminergic cells systems off our body. When we start to age, concentration of these neurotropins both in the brain and the muscles start to decline and that leads to decreased neurogenesis, accelerated muscular atrophy and that can lead to impairment in both cognitive function and physical activity. Aging can also lead to exhaustion of stem cell population and and various stem cells can exert neuroprotective effects and enhance function function recovery by bringing in more of these neurotropic factors. And there's this T bar byproduct lipid peroxidation also significantly increase as we age and that also further impairs our functions. And when they use adipose derived MSCs in Alzheimer's mice model that has showed that these MSCs can increase brain concentrations of acetylcholine, brain derived neurotrapic factor and nerve growth factor and that can improve cognitive function and physical function in aging mice. And then adipose direct mics also can secrete a very high concentration of vegf, which can contribute to Prolonging the lifespan of these mice. And in an ALS mouse model. And then interestingly also if you get stem cells from the muscle, it can also achieve some of these beneficial effect. And in this experiment they did aged mice which is 10 months old. So these very common rat model, they divided into control group, a amniotic membrane group and adipose derived stem cell transplant group. So two groups have stem cell stem cell transplant and they used young mice seven weeks old as control. And they gave 1 million of either human amniotic membrane stem cells or adipose derived MSCs. And they were giving them intravenously once a month throughout the rest of their lives. And both stem cell group actually improved the cognitive and physical function of these mice by about 23 and 31% respectively. By the time the rats have reached 20 months of age. In the control group, only 30% are left. But in the treated group with both, you know, with stem cell stem cells is about 70% and 100% of the mice are still alive. And by 23 months of age all the rats in the control group have died. But when they died, Have died. But in the stem cell treated group, the survival rate is about 60 and 72% respectively. The transplanted cells were found to differentiate into neurons and that they the differentiation also is about between 50 to 75% rate. And the brain derived neurotropic factors have also been upregulated in these transplanted group to a level that's higher than in young rats. So you give them this extra benefit is actually higher. And also muscular neurotropic factors were also restored in these transplanted group and to a level also higher than in the younger rats. The transplantation significantly increased the number of blood vessels that's comparable to the young rats. So that's pretty exciting. The tissue injury was nearly fully attenuated in these transplanted group. And monthly transplantation have increased both the stamina and cognitive capabilities of these aged rats. And acetylcholine levels in the CSF and muscles have restored after the transplantation. And there's also, when these, when these cells age, there's alteration in gene expression and these were also restored. So actually there's a genetic modification factor. And when the cells, when the age rats, you know, when they age to a certain point. So in this experiment they only have about 27.8% of the stem cell reserve as young rats. But after the stem cell transplantation they have increased the level that's comparable to young rats. So you're restoring the stem cell level and certain Chemokines that are suppressing neurogenesis that has also been reversed. So you're removing these detrimental factors. So basically if you look at, in general, these have shown that stem cell therapy can increase concentration of acetylcholine and recover neurotropic factors in both the brain and the muscles. And it restore not only their function, but also the microvascular formation and so restoring the function of these older rats. And here's another study that we're looking at these. You know, I really like the study because really interesting, especially with the human correlation. So they're looking at mice who are at 15 months of age, which is human equivalent of 75 years old, when 50% of their peers have died. And at that time they start giving them stem cells. They give them 100 million of nucleated cells from bone marrow from young donors, from young, young animals. And they repeat that six times within three months. And they used mice age 3 to 15 weeks as the donors. And the result is that the maximum lifespan in these mice that are human equivalent age of 75 years old, right. They actually increase the lifespan by over 30%. And the survival time from the beginning of the experiment to the end of experiment, basically the mice that got stem cell transplant lived 3.2 times as long as the mice that never got stem cells. And at 19 months, the last of the control of the mouse died. And it's kind of sad because they died sedentary, almost immobile, and they were hunchbacked with poor. But the mice that were transplanted with stem cells, they were still active. Their spine is even, they had shiny, even hair. So you know, what a, what a, what a hopeful picture for aging adults. Right. And the observed lifespan extension is accompanied by extension of healthy life, you know, health span, basically healthy life period. And there's also some chimerism going on at about 28%. And, and this result is highly encouraging for humans. And here's another study looking at transplanting human cord blood stem cells in treatment of inflammatory conditions. So there are 20 patients that are treated for chronic inflammation. They have conditions such as osteoarthritis and inflammatory back pain, shoulder, herniated disc, so on. And these are used predominantly for anti aging purposes. And they use IV infusion of cord blood cells. And the patient, 10 of them actually showed improvement in their, you know, kind of the basic labs. And then anti aging benefits were evaluated at one day, two weeks and three months. And at three months they show significant improvement in skin, hair and nail growth, energy levels, libido Mood, sleep, and pain levels. And then the last thing I want to mention is about stem cell therapy for aging frailty. So frailty is a big problem. Increases the risk of falls, hospitalizations and disability and death. And there's certain index to evaluate aging, frailty. So the prevalence of frailty in elderly is over age 65 is 7 to 12%. But if you look at pre frailty, which is people who had met one to two out of five criteria, is actually 35 to 50%. That's a huge percentage. And these are very much associated with comorbid conditions, even when they're just pre frailty. And then when they did stem cell therapy. So before I go to the stem cell treatment, what they found is that there's a strong link between the stem cell decrease in number and function and their frailty and their inflammation level. And aging actually induces what's called quiescence to senescence switch of the stem cells. So it changes in the extracellular matrix, so in the whole environment, the cells. And that also reduces stem cell self renewal, maintenance and regenerative potentials. So these has significantly contributed to the frailty symptoms. And that intravenously delivered. Okay. Two minutes delivered. MSCs are safe and can produce these improvements. So there's more studies. Phase two, Live happily, live long. And if you want to reach me, that's my contact information. Whoa. Okay.

All right.

That was what a finish.