Evidence Behind Stem Cell Therapy in Diverse Disease Conditions

These probably are the mechanisms why stem cells can help autism cases. So it can help improve angiogenesis, modulate the immune system, can reduce apoptosis, so reduce cell damage, antioxidant effect, modulate the excitation response, restore neuro connectivity. I think the purpose of this is really to talk about what kind of evidence is there. You know, we're all passionate about stem cell treatment, but what I've always been focusing on is what kind of evidence I can present to my patients and is actually pretty impressive how much evidence is out there. So what I have prepared, it's going to be a lot of slides, so I'm going to just be zooming through them. But I just want to give you an idea of what's out there and what kind of conditions have been studied. So you can take that back into your clinic and really, really help, you know, make some differences in places where maybe you didn't know that there's some evidence about stem cell treatments. So, yeah. So I founded American Academy of Integrative Cell Therapy. I do, we do have a clinical course called Fundamentals of Stem Cell Practice where I go into more detail. But let's start. So first of all, autoimmune condition, that's the one condition we know that, you know, one category we know that stem cell therapy has been powerful in. And let look at first, lupus. So this is using umbilical cord mics in severe refractory lupus patients. So 16 patients, there is significant decrease in disease severity and including improvement in markers and reduction in disease activity achieved in all these 16 patients with no recurrence three years later. So that's pretty impressive. And here's another study. 40 patients using umbilical cord mics in active and refractory lupus patients and they were able to see major clinical response in 32%, partial response 27% and no response in 40%. And at nine months there's some relapse rate and at 12 months, you know, about 16% relapse rate. So their conclusion is that you likely require new infusion in about six months. And rheumatoid arthritis. So this is a study again using umbilical cord MSCs for people with active rheumatoid arthritis. And there's significant remission in all the MSC treatment groups, including improvement in their sleep diet, physical strength as soon as two weeks post treatment and joint swelling were alleviated even within 12 hours and maintained throughout the study. Here's inflammatory bowel disease. Traditionally we were using hematopoietic stem cells to treat patients. But that has various drawbacks, partially because you require chemotherapy and antibiotics and steroid. It just there are a lot of side effects. And the new approach, probably a better approach, is using mesenchymal stem cells and you can do it locally or systemically. So here's example of perinatal fistula and local injections were able to help achieve 85.7% successful success rate in the healing of the fistula at 12 weeks. Another example for Crohn's disease, using IV bone marrow derived stem cells, they were able to achieve.

An end point that indicates remission in 148 out of 207 patients. So that's quite impressive for Crohn's disease. Here's another study, 82 patients, they were given IV infusions of umbilical cord stem cells MSCs. At 12 months they showed significant decrease in their symptoms and also decrease in the steroid dose. Here's a visual picture of what you can see in the mucosal layer and the improvement in the tissue scleroderma in refractory scleroderma. This is only case study.

They were using umbilical cord mics and looking at actually patients achieving.

Remission and they were able to sustain results for 12 and six months. And the second treatment, when they, when they did it, they actually did not use any, any medications, any plasmapheresis. So they just gave stem cells straight and that still worked very well. Cardiovascular condition I'm going, going fast because there are a lot of conditions so atherosclerosis, these are so some studies, mice were treated with MSCs and they were.

Reduction in the plaques and also inflammatory markers and they were able to reduce cholesterol and able to reduce the vascular lesion by 33% in the aortic route. Here you can see a visual lesion size decrease and macrophage content decrease at the site. Myocardial infarction Human umbilical cord blood transplanting. So this is a first one is a mice study. They showed reduced infarct volume we with 20% higher capillary density around the infarct area. So that shows, you know, recovery of the tissue. 2006 rat study Umbilical core blood cells was able to colonize in the infarct area.

And what's fascinating, this is a rat and they showed the cells around the blood vessels were actually of human origin. So they were actually settling down in a different species and still was able to help, you know, you know, help.

The regeneration. And the ras study in 2009 also showed, you know, some correlation with higher VEGF levels and the cells were able to concentrate in infarct area. So their conclusion was IV infusion actually was a adequate strategy for treating the heart.

Okay, I'm sorry, I went back. Okay, here's another study looking at mscs, how it helps the recovery in breaking down scar tissue after MI and two months after MIC treatment, the ischemic heart showed large improvement in left ventricular anterior walled thickness in the infarct area and of course the ejection fraction was improved. And congestive heart failure.

Intravenous infusion of umbilical cord. MSCs in heart failure of patients were able to show that the treatment group was improved in left ventricular function and quality of life at 3, 6 and 12 months follow up.

It decreased their hospitalization and decreased their arrhythmic events. Here's another congestive heart failure, some more studies showing the allogeneic cells actually increase left ventricular ejection fractions significantly and MSCs from either adipose or bone marrow do not increase the left ventricular ejection fraction compared to controls. So in this case the allergenetics showed a higher efficacy. And mscs actually when you give it either around the heart, right around the heart, or intravenously did not show that much difference in the improvement. So that's really interesting. And then this is why I'm so excited and you know, because it's such an elegant approach to give people an IV treatment because I do count on the natural intelligence of the cells to find the areas where they're needed. And we can see more of the evidence as I go through other organ systems. Diabetes. So type 1 diabetes, 29 patients, newly onset type 1 diabetes, they were given two infusions four weeks apart and they were able to show improvement in hemoglobin A1c and C peptide in, in these patients comparing to before the treatment or comparing to placebo group and another study using Wharton Jelly msc and they were able to show that these MSC could, even though they're called mesenchymal stem cells. Right. So they're supposed to be from mesoderm layer, but they can cross this, this germ layer, you know, differences and, and differentiate into insulin producing cells. So that's pretty cool, pretty exciting. So after MIS C transplantation, what's fascinating is that some of these insulin producing cells were located in the liver and still, even though they were in the liver, they were still able to normalize the hyperglycemia and Wharton's jelly MSCs can be differentiated better than bone marrow MSCs toward the mature beta cell type and type 2 diabetes. So this is study showing 22 patients given IV injection plus intra pancreatic injection and they were able to using umbilical cord, I mean Wharton Jelly MSCs, they were able to significantly decrease the level of blood Sugar and hemoglobin A1C and improve C peptide levels, showing that there's better beta cell function and reduced marker of systemic inflammation. The hemoglobin A1C level was lowest at 3 months post treatment, but the improvement was sustained at 12 months. So that shows the long term benefit of these stem cell treatments. And here's another study. Adult allogeneic bone marrow derived MSCs, MSC precursor cells. So this is something that's similar to mscs. They when compared with placebos, these, the patients who were given the stem cells were able to reduce hemoglobin A1C.

So just more proof and then we come to neurological. So hemorrhagic stroke, we can use intravenously transplanted human umbilical core cells which when they were given intravenously they could migrate selectively to the area of the lesion and result in better functional test performance in seven and 14 weeks. So again intravenous, the cell's intelligence will guide them there. And for here's an ischemic stroke using autologous bone marrow MSCs and they were able to show functional recovery more frequently than control. And the cumulative survival rate was much higher, so twice as high in the treatment group than the control group. Spinal cord injury, we're talking about spinal cord injury. So here's a study on umbilical cord derived stem cells. 25 patients, they were given both intravenous and then later on intrathecal. So at 12 months after treatment.

There'S some improvements. So I wish it's higher, but I think in spinal cord injury cases the expectation is more tempered, which was why it's so exciting to see what they were doing in China. So here you can see 16% showed improvement in this American Spinal Injury association score and spasm decreased in 28% of patients. And then autonomous function improved in 32% and there's some 24% had improved urinary function. And in traumatic brain injury, MSCs do have the ability to cross the endothelial layer, so cross the blood brain barrier. So a lot of people don't know, they think that MSCs, because there are cells, they're stem cells, they can cross the blood brain barrier, but no MSCs actually have a particular capability to, to integrate into the endothelium and then cross the layer. And so they were able to influence the tight junction barrier and they're able to decrease inflammation. So this is an important property of MSCs. So here's a lot of preclinical studies showing bone marrow mononuclear cells improving TBI outcomes. And in a phase one study of children with severe TBI they were showing that there is not only safety but also central nervous system structural preservation type of effect. Another study of 25 adults with severe TBI and this is within 36 hours injury, they were able to show that with stem cell treatment there were structural preservation at critical regions that were correlated with functional outcome. And they also were able to downregulate inflammatory biomarkers. And when infused intravenously these cells are able to have similar mechanisms of action, whether or not so, you know, by, by dampening the innate immune system. So I think we just need to, you know, keep in mind that the power of IV infusions because not only it will travel to the site of injury, but it's also going to talk with your entire immune system and invoke the help of your spleen and your peripheral lymphoid system. So I don't think we can underestimate the power of your entire body instead of focusing on local injection. This is why I think even for central nervous systems is, you know, intranasal is a great method but I think it's important to still bring the power of your systemic, of your entire body into place.

Another study, this is an animal study, MSCs can selectively migrate to injured brain areas and differentiate into neurons and astrocytes. So that's another thing that you know that even though they're mesoderm cells, right, mesenchymal stem cells, but they can differentiate into neural tissue. And another study showed that after MSC treatment, the different growth factors, the nerve growth factor, brain derived nerve neurotropic factor, were Significantly increased during 6 month follow up and correlating with neurological function improvement. Migraines. These are very severely ill. Patients sometimes have daily or even twice daily migraines. This is small study, only four women, they were giving them IV stromovascular fraction and all experienced dramatic improvements. Some required repeat infusions seven to 18 months after. And then another study had nine patients and they also show some benefit but they were doing IM injections So these did not produce as profound of an effect as studies using IV spf. So I think that probably speaks to the Power of the intravenous method, orthopedic conditions. I love this study because it's so powerful. Okay, so basically 30 patients, they all had steroid induced.

The osteonecrosis. So bones are going dead in both knees. So they would need typically bilateral knee replacement. But what they did was they divided the patient from the center line so they would do one knee replaced the other knee inject, I think bone marrow derived stem cells and look at the outcome. So what happened was really fascinating is that at 12 year follow up, six of the 30 total knee replacement patients actually needed a revision surgery. So still, you know, six out of 30, that's one fifth. But the knee that only got bone marrow derived stem cells, only one actually needed surgery at all. So this is a very powerful study. Degenerative disc disease. So some studies have shown that MSCs can restore disc height and function and improve symptoms. Another study was looking at 10 patients, autologous expanded MSCs injected into the nucleus and showed rapid improvement in pain and disability. And so umbilical cord MSCs, they actually could induce synthesis of proteoglycans and restore disc structure. Avascular necrosis.

Stem cells. So whether or not it's early disease or later stage disease does have something to do with how patient, how well they do with stem cell treatment. So if it's early pre collapse type disease, in avascular necrosis of the hip, you know, of the femoral head, only nine out of 145 of those hips actually required total knee hip replacement. But if it's later stage, then you know, more than half will ended up require total hip replacement. Ankylosing spondylitis, these are of course inflammatory disease and you know, there are suspicions that they actually have dysfunctional msc. So these patients have impaired immune regulatory capabilities. In these 31 patients, they gave them four IV infusions and the response rate was 77% at fourth week. And MSCs were obtained from bone marrow and of a young male. So that's very encouraging. And then we go on to reproductive organs. So premature ovarian failure. In preclinical study of animals, the stem cell based therapies actually improved all the markers fsh the estrogen level, ovarian weight, follicle count and number of pregnancy. So this is very encouraging for some of my female patients. And after MSC treatment the when they looked at the ovarian size and endometrial thickness, they all have improved in aging ovaries. So these are premenopausal rats and they were giving them either stem cells or control through IV route. And they also showed decreased FSH and improved ovarian structure with increased follicle number.

Erectile dysfunction, we're all very familiar with the treatment of this. All the animal studies have shown improved function and erectile dysfunction, whether or not it's caused by.

The penile injury or vascular insufficiency or diabetes or hyperlipidemia or just aging. One study shows seven men given umbilical cord blood stem cells, six delta seven returned their early morning erection in two months and also increased penile hardness. And they were able to respond to, you know, Viagra where they couldn't respond to it before. Another study show bone marrow derived mononuclear cells also were able to help people with vascular genic erectile dysfunction. So nine out of 12 patients was able to achieve successful intercourse. So that's, you know, that's amazing for these patients. Another study, 17 men refractory post prostatectomy erectile dysfunction. They were given autologous adipose derived stem cells and show significant improvement noted at six months. And this is really important even though they didn't see any improvement at one and three months. So tell patients to hang in there. Just because you didn't see anything one to three months doesn't mean that hope is not down the line. And some other studies also substantiate similar results. And diabetic erectile dysfunction. So similar.

These are older patients, average age of 69 and they failed to have erection despite medications. And they were given umbilical cord blood stem cells. And within one month morning erections were regained in three patients. So these are out of seven. And by the third month six out of them have regained morning erection. And also with increased rigidity and desire and with improvement in blood sugar and decreased medication dose. So hemoglobin A1C is improved. So it treated their erectile dysfunction and diabetes and peyronie. So this is an inflammatory plaque forming disease with curvature of the penis. And local injection using placental matrix derived MSCs were able to so right around, in and around the plaque and they were able to. Out of the total 10 plaques, seven disappeared completely at three month follow up. And I have that clinical experience as well, you know, very simple injection and complete resolution of the curvature so kidneys renal failure. In preclinical studies they were able to show that for type 1 diabetes mice a single IV dose MSCS led to recovery of renal function and pancreatic function. And some studies also showed that bone marrow derived MSCs can reduce the effect of Ischemic renal injury. And even though MSEs did not really quite integrate long term into the renal tubule cells, but they were able to help repair.

The renal system through the complex paracrine and endocrine function. So this is why I'm not stressing, you know, whether or not the cells are identical to the human to the person, the recipient is not crucial because we know nowadays with mountains of evidence how these cells work because so much of it is through paracrine and endocrine function, because they function in the body as a signal. Not exactly going to the place to differentiate. But even for differentiation, as you've seen, human cells can differentiate into, you know, of course can differentiate and, and organ cells and survive in the animal body. So even cross species is not uncommon, but cross humans is very common. I don't know if, you know, we 60% of women actually carry Y chromosomes in our body. So between human, you know, within human species, having other people's DNA is really not something that's that dramatic and that incredible. It's part of human history.

Another.

Example, this is just a case study. 60 year old woman, she had chronic renal failure, but she also had spinal cord entrapment.

Her creatinine level was 11 with no urination and she was given umbilical cord mics intrathecally and also intravenously. Three weeks later she was able to move her toes and her kidney function improved and her creatinine level came down to nine. And after eight months her creatinine was two and she had normal urination. Okay, moving on to liver. So liver cirrhosis. So this is an animal model, rat liver fibrosis model. And rat was given human umbilical cord cord mscs and they show significant reduction in liver fibrosis. And the engrafted human cells scattered, you know, in the tissue but did not differentiate into hepatocytes. So they didn't become liver cells. But they were able to secrete all these bioactive cytokines that restore liver function.

The end stage liver cirrhosis. So these, this is a human study. 51 patients, 2/3 had ascites and 1/3 had hepatic encephalopathy. They were given them human umbilical cord blood cells. And after a single cell stem cell treatment, most of the he encephalopathy patients and more than 2/3 of the CITES patients improved in symptoms or responded to medical medication therapy that they were refractory to previously. They also improved their life expectancy. Lungs copd. I love treating copd. Patients because the results are so remarkable and it's so fun because that's the first place the cell go to. And all this talk about the lung trapping it just silly because initially, yes, it's well perfused. So the cells are going to be in the lungs and the liver in the spleen, because that's you, that's where most of the perfusion is. But the cells are not dumb. So they don't stay in a place where they're not needed. They will go to places once if the lung is normal and healthy, it's going to migrate and it's been shown to migrate systemically into other areas. So you don't have to worry about the lung trapping unless your lungs are really needing help. So in this study, intravenously or intraperitoneal injection of, you know, again, human MSCs into rodents, they show significantly reduced airway inflammation, parenchymal lung cell apoptosis and also collagen deposition. So less fibrosis. And intravenous infusion of autologous bone marrow cells into COPD patients, only 4 cases, 12 month follow up showed significant improvement in the quality of life as well as slowing down of disease process.

A lung injury model, umbilical cord MSCs were used and they were given systemically.

So injected MSCs were located in the lungs two weeks later only in areas of inflammation and fibrosis. Again, they don't go and sit around in healthy lung tissue. They find the place where they're actually needed. And the administration of these MSCs reduce inflammation. They have antifibrotic properties and I sort of. So this is retinitis pigmentosa, you know, usually a very, very, you know, considered permanently, you know, permanent disability. So they were able to inject intravenously into this rat model of retinitis pigmentosa. And these injected cells from IV route migrated to the eye and possibly attracted by the chemokines and you know, secreted by the, the retina. So visual function were actually significantly preserved comparing with controls. And then, you know, it's demonstrated there's neuroprotective effects from these cells and also growth factors were upregulated. So there's a protective neural protect effect in glaucoma.

Bone marrow derived MSCs were able to provide survival of retina ganglion cells in the transplanted eye compared to the control. So they were testing their ability to swim in these rats. And these transplanted rats, you know, when they got bone marrow derived MSCs were able to perform much better. So again they show bone marrow derived stem cells is protective in aged rats with retinal ganglion cell loss induced by glaucoma macular degeneration.

So mscs. So.

In this article they were basically shown to secrete these growth factors and they can provide neuroprotective effects and they can either inject into the eye or intravenous and they could both achieve the retinal protective effects. And intravenously injected MSCs increase the survival of the photoreceptors and restored visual function by these rat models. And and so it effects again was attributed to the secretion of these retinal neurotropins by the mscs and then they also down regulate, I mean upregulated the, the anti apoptotic gene so preserving some of the cells.

Years. So hearing, hearing, loss, sensory, neural, hearing loss. They were able to show using IV umbilical cord blood drive stem cells can enhance hearing threshold. And the systemic infusion of human adipose derived stem cells significantly improved hearing function and protected hair cells and skin.

This is just one example apoptotic dermatitis but they're not as many studies on skin. This is atoptotic dermatitis. 34 patients, they were given the stem cells, umbilical cord blood derived stem cells subcutaneously and there is a dose dependent improvement. And they were able to show that the high dose of the MSCS were able to reduce the pruritus score by 58%. So they did downregulate the IgE levels. Graft versus host disease so you guys all know that stem cells MSCS is powerful when it comes to graft versus host disease. And what's fascinating is that even when there's.

So I don't know if you probably all know that even if you perfectly match so humanly matched cells or humanly matched organs can still have a significant rejection rate because we're not matching all there is. You know, we're matching what we know. But they were able to give MSCs which is completely unmatched and that was able to reduce rejection rate and help reduce these graft versus host disease. So that shows you the power of the mscs that not only is immune evasive but is immune suppressive regardless of HLA compatibility.

Another study showed that 70% response rate overall and the complete response rate at 28 days was 77%.

So and then here we have a study on HIV. It's very interesting. So these are people who are not responding to these, you know, antiviral medications. Thirteen patients, they're not non responders. And they were given three umbilical cord MSCs.

Transfusions, and they were able to increase the patient's CD4 cell count and reduce systemic immune activation and inflammation. So that is, you know, incredibly helpful for, for these people who otherwise was probably losing hope, autism.

So these probably are the mechanisms why stem cells can help autism cases. So it can help improve angiogenesis, modulate the immune system, can reduce apoptosis, so reduce cell damage, antioxidant effect, modulate the excitation, you know, response, restore neural connectivity, stimulate endogenous stem cells. And here's a article about the so talked about, you know, 2013 studies showing some improvement in kids being treated with stem cells, showing improved eye contact, social interactions, emotional responsiveness, speech and communication sensories, you know.

Sensory, I guess, perception, attention, concentration and hyperactivity, aggressiveness. So there are plenty of studies showing more, you know, very similar results. And a study in 2013 using umbilical cord.

Both umbilical cord stem cells, umbilical tissue stem cells, and umbilical cord blood stem cells. What's interesting is that I love to study the fact that they were looking at cord blood, mononuclear cell group and cord.

And then a combination group and a control group. They did four infusions, and they showed that the combination of the cord blood plus the core tissue MSCs are the most powerful, have the best effect. So I always believe that we want a comprehensive cell type. We want to bring the synergistic effects of these cells together.

And this is another study I love, you know, we don't have a whole lot of good treatments, you know, of alcoholism. I was a medical director for a few rehab centers in Malibu, and I've seen how difficult it is. And this is a really powerful study. They were looking at these alcoholic rats and looking at how stem cell infusions can change their drinking behavior. So they were giving them just free alcohol, 10% for 73 days, and then another 27 days of access to 10% or 20%, you know, drink as you wish. And then they give them.

They actually inject into the cerebrum. So they injected into the brain of these bone marrow derived MSCs or adipose derived MSCs, and then they were allowed to drink either water or alcohol. And they showed a significant reduction of alcohol intake. And then they showed that. So a single dose MSCs were able to reduce the alcohol intake by 50% for 10 days. So that's pretty remarkable. And the second part of the study is really fun because they're really mimicking the rehab situation, they let these rats drink and drink and then all of a sudden they deprive them for 14 days. So it's like putting them in rehab for 14 days. So on day four of the deprivation, they give them either stem cells or a control, you know, placebo. So after 14 days, they led them to free intake alcohol. So they record how much alcohol they drink in 60 minutes. And they were able to show that MSC infused rats were able to drink about 80 to 85% less. So this is remarkable. And their suspicion is that alcoholism is driven by neuroinflammation by decreasing the inflammation in the brain that you drastically reduce the drinking, the, the, the addiction behavior.

And the last one I want to talk about is anti aging. So last year I actually did a presentation specifically on anti aging benefits of stem cells. And this is area I'm passionate about because I want to help people to prevent the decline and to continue to be vibrant. So I'm just going to give a few examples. Of course, anti aging when you study lifespan is very difficult to study in people. So you want to study in animals. The results has been pretty consistent. We're able to see that the maximum lifespan in the stem cell treated mice were able to be increased by about 30% and the survival time were able to be increased by 3.2 fold. These are older rats. When they start giving them stem cells, even when they're older, is giving them the remaining time, extending them basically lengthen them by three times. So that's, you know, gives a lot of hope for people who are much older. But you're going to have a lot more time left and not only longer time left, but it's also better health span. They look a lot better, they're smarter, they're more active, they just, you know, they're, they're more vibrant and there's some chimerism. So which means the stem cells did integrate with a new organism. And that's, to me, that's fine. Another example age rats. So 10 months old. So they just, you know, middle aged, they're aged and then they were giving them intravenous stem cells and they again showed about, you know, 23 to 31% extension of their lifespan. And not only lifespan was extended when they examined their brain and their muscles, the brain neurotropic factors and the muscle neurotropic factors both have been restored to a level higher than the younger rats rats. And when they look at their number of blood vessels, the number of blood vessels restored to equivalent to the younger rats. So everything was restored to the younger state.

So here is actually a human study looking at 20 patients. I think this is conducted in China, looking at effect of anti inflammatory effects and anti aging effect. Just one infusion and then they measure some markers. And then at two weeks, three months, they look at how they did. There's improvement in skin, hair, nail growth, energy level, libido mood, sleep and pain level. So that's, that's it. There could be a lot more. But, you know, there's only there are only 20 minutes. But I encourage anybody that's interested to to take the, you know, American Academy, aict.org so the course is on there as a very comprehensive course. You get to take home over 300 articles. And then, you know, you get different protocols. And, you know, a lot of support from me.