How Stem Cells Work: Mechanisms of Regeneration and Repair in Medicine

Hi, this is Dr. Joy Kong again. I want to continue our discussions about stem cells and regenerative medicine. Today. I want to talk about how stem cells work, because I think there are a lot of ideas about how they work, and there are some big promises and claims, and I just want to give people the nitty gritty of exactly what the mechanisms are. So when we talk about stem cells, really, a lot of times we're talking about mesenchymal stem cells. So these are what I call the masters of regeneration. So the. These cells are actually all around your. Your tissue. So in every tissue that has been vascularized, which means having blood supply, these cells are there because they huddle around blood vessels like, you know, almost like, you know, forming like a. Like a gecko, you know, on. On a wall. They're holding on to it. And when there are signals that. That they can sense, they often traverse, you know, they. They squeeze into the blood vessels and they swim upstream to the. To the location of information, which are either signals of injury or inflammation. Those attract these cells to get to the area so they can do their work to promote repair, regeneration. And when they're sitting along the blood vessels, they also kind of have their pulse on the local cells, including the local stem cells. So they talk with the stem cells all around them, and then they are sensing the signals from the blood. So that this is kind of the general idea of what these cells are. And they have this role of conducting the symphony of regeneration because they're everywhere in your body. So even though they're called mesenchymal stem cells, there's still some. You know, a lot of scientists are not liking the word stem cells very, very much. Some clinicians, because they think that these are not the tip, in the typical sense stem cells, because they don't. Their main function is not to differentiate into different cell types. Their main function is to coordinate this regeneration. So mesenchymal stem cells in the petri dish, they can be induced to form this cell of the lineage of the mesenchymal lineage, which means that they can be induced to form cells, you know, muscle cells, you know, bone or cartilage or fat. But when the mesenchymal stem cells is very young, they actually have been induced to form more cell types, including neurons. But anyhow, so. But their main function is to send out signals, is to tell your body to come and do the repair and talk to your local stem cells so they can differentiate and replace the tissue. So that particular function is what's called paracrine effect. So paracrine as opposed to endocrine. Endocrine is when a molecule secrete into your blood and it has a global effect. Paracrine means in a local environment, so the cells send out signals to the local area so that the signals can induce changes in the smaller confines, you know, smaller environment, so they can send out signals. So once they traverse into the blood vessels, they get to the local area of inflammation or injury, they can promote immune cells to come in to clean up the area and to mount a, you know, either inflammation, which is important for, you know, for, for clean, cleaning up problems, and then the anti inflammatory part of the, the regenerative process so they can talk with local cells and then have them to come in and do the rebuilding of the damaged tissue. So that's a paracrine effect. But there are many mechanisms of how these mesenchymal stem cells work. They're kind of the, the new golden boy on the, in the, you know, in the field of regenerative medicine because they are so crucial and they're able to do so many things. So what are some of the things they do besides this paracrine effect? So one thing that people talk about a lot, one of the main mechanism is anti inflammatory effect. So they calm inflammation. And inflammation is a driving force of diseases, especially chronic diseases and aging. So there's a word coined inflammaging, so inflammation actually driving aging. And they're kind of hand in hand, they are together driving the aging process. And the aging process really is the prequel to disease. So even though you don't see the disease yet, but that's how diseases start. It's the deterioration of your system and then the disease is the eventual outcome. So you can look at disease as a house, let's say your body as your, as a house. The disease is really the house caught on fire. And then you see the smoke coming out when you're, you know, looking from the outside is, oh, okay, so there are symptoms, you know, things are manifesting. But before the house is caught on fire doesn't mean that things are not going on. Right. Just because you can't see doesn't mean that little things are not catching on. You don't see the smoke yet, but things are happening before the smoke comes out. So that's what inflammation has been in the aging process. Right? The aging process, inflammation, they go hand in hand and they drive the disease process. So if you can calm the inflammation, then you can slow down the disease process or prevent the disease from happening. The, so anti inflammatory Effect has been shown over and over and over in stem cell therapy because it can reduce inflammation. And when you keep inflamed, when you stay in inflammation you cannot repair because your body's in this acute state, the repair cannot really happen. The regeneration cannot happen. So that's anti inflammatory effect. Another effect is immune modulation. So the inflammation is really this inflammatory aspect of your immune system. And then there's an anti inflammatory, inflammatory action of the immune system. So it's called T1 and T2. So there should be imbalance. But as we age, we are more inflammatory than anti inflammatory. So the balance is tipped over. This is why when a person seems like in perfect health, you know, a person's aging, but this older person looks like he's in perfect health. But guess what, if we check their inflammatory markers, their inflammation markers higher, so it doesn't matter how nice and well aged they are, they're still are going down the inflammatory path. And so if we can prevent that from happening, then we can bring, bring back, you know, the immune balance and dial back the inflammatory, you know, that, you know, bring it down, then we can keep the person in a more youthful state. So the stem cells has the ability to do that. And one of the major benefits that has been seen in research throughout the world is how it can help with autoimmune conditions because they can, you know, shift the balance, make somebody from this highly inflammatory state into the anti inflammatory state. So that's the immune regulation aspect. And then there's some other really interesting benefits of stem cell therapy. For example, mesenchymal stem cells can actually promote angiogenesis. So angio, that's, that's the blood, you know, angiogenesis, blood vessel formation. So let's think about something. You know, let's say a stroke. And if you can promote blood vessel formation, you can reestablish the, the blood flow, then you can nourish the tissue again. Right. Or you have a damage somewhere and you can rebuild the tissue. But if you don't have adequate blood supply, the tissue is not going to survive very well. So the angiogenesis is another way that these cells can help the body repair. And then there's a property called anti apoptotic. So apoptosis is programmed cell death. That means there's a particular pathway. When the cells receive that inflammation, it will go down the death pathway. So it's gonna just, you know, spiral down, eventually leading to death. So when would that happen? Sometimes when the person has a, has stroke. Right. So the particular area of the Brain has blood supply cut off, but the surrounding area, even though the blood supply has not been cut off, what happens is that the dead tissue can send out signals all of a sudden telling the neighboring tissue to die. So giving them the signals to tell them to go into apoptosis. So instead of just having this area that's, you know, without blood supply that dies, the neighboring healthy tissue can start to die. So that's, we don't want that. Right. So that can happen with, you know, mechanical injuries, with chemical injuries, radiation injuries. So the neighboring stage, supposedly healthy cells that wasn't affected ended up dying. So stem cells can help protect, that can help basically say you don't have to die, you know, let me give you other signals and can reverse the pathway. And you know, on the other hand, what's really interesting is that stem cells actually have the intelligence when it's tumor, when it's cancerous, cells, especially younger stem cells have the ability to, ability to tell that these cells are abnormal and not good for the body. So they will actually send out signals to tell them to go on to apoptosis, to tell them to go on programmed cell death. So the cells are not just blindly, you know, saving other cells. If the cells are dysfunctional, are not supposed, supposed to be there, then the stem cells, the mesenchymal stem cell cells, are able to tell that we need to make sure these cells die. What's fascinating is the older we get, the less that ability is still there. They've done experiments where they compared stem cells from umbilical cord, which is very young source, and stem cells from somebody that's middle aged, and they use the fat derived stem cells and they look at the young stem cell, young mesenchymal stem cells versus middle aged mesenchymal stem cells from fat and look at their effects on cancer. So on tumor. So they did it both in a petri dish and on a live animal. They put the stem cells next to the tumor and see how the tumor respond. So when it's fat derived stem cells from a middle aged person, they realize that either in a petri dish or on an animal, the tumor grew, they grew more. But if you use umbilical cord derived mesenchymal stem cells, the tumor actually shrink and start to disappear. So this is very fascinating because not all stem cells are created equal. So I actually have a very technical lecture that I put on YouTube. It's called are all MSCs created equal? It goes to extensive details about the comparisons between different stem cells. But this just shows you That a younger cell can have the intelligence that gets lost when a cells age. So stem cells, just like any other cells in our body will age. They have gone with us on this life journey. They have been exposed to same kind of toxins. They have endured oxidative stress in their body. So they will have changes, their DNA may change. So they senesce. Our own stem cells over time will become less and less potent and less effective and they have less ability to produce anti inflammatory, you know, signals and less ability to differentiate. So they deteriorate. So that's anti cancer effect will get less and less as you age. And this could be another reason that we have higher and higher rate of cancer besides just the aging process of changing cells. So another benefit which is really interesting is what's called antifibrotic effect. So mesenchymal stem cells have been shown to have anti fibrotic effects, which means breaking down of scar tissue. So scar tissue is a, it's a problem in various diseases including lung fibrosis, right. COPD and your lung tissue start to become fibrotic, so it loses function, it becomes this hardened connective tissue. So then the lung is not working very well. Liver cirrhosis, same thing. The fibrotic process starts to set in or some condition. This one condition called Peyronie's. So that's a condition of the curvature, abnormal curvature of the penis and that's an inflammatory process, that's because of plaque formation of the fibrosis. So the penis is curving and the stem cells and I have treated patients with this condition and with one injection actually the penis will straighten. And I've given treatment to people with liver cirrhosis and with copd and it has pretty incredible results. And part of it I do believe is the anti fibrotic benefits. And then what's interesting is that these mesenchymal stem cells actually have direct antimicrobial benefits. So they can not only just boost your immune system to amplify their ability to, to fight infection. These mesenchymal stem cells have been found to directly secrete these antimicrobial peptides so they can actually kill these microbes on their own. So that's pretty cool. And another thing I want to talk about, stem cells is that these new fresh stem cells that's been transplanted especially from the umbilical core source, which I believe is the best source. Just listen to my lecture. You will see this backed by lots of scientific studies. So these are better sourced than an adult person's own fat or Bone marrow. So these umbilical cord sourced stem cells, they also have fresh young mitochondria. And what's fascinating is that these cells will actually do what's called mitochondria transfer. So when these are transplanted into a person and these cells actually have established, can establish microtubule bridge. So you know, connecting themselves with your own cells and then the mitochondria actually can walk across the bridge into the new cell. They've caught this on electron microscopy. So this is pretty fascinating. So in a sense you're getting a fresh new mitochondria supply and we all know mitochondria is crucial in our health and, and it has become a huge, you know, topic in healthcare and how the decline of mitochondria is affecting everything in our body because they are the engine of cells, right? If your cells don't have the energy to work, then it's sluggish, then nothing is going to be very good. So you're getting fresh new burst of mitochondria. So you can imagine how that can revitalize a person's health. So all these are some of the mechanisms and I just feel that there's a need for people to understand how profound these cells can help the human body is. It's it. There's particular, there are particular ways that they work which are really fascinating and really fun. And I want to talk about how there are stages of repair from the cells. When somebody gets stem cell treatment, there are different stages of improvement. The first stage is very fast, is the anti inflammatory and removal of dysfunctional cells, kind of cleaning up the debris type of action. So that's much faster process. So a person, that's why, you know, when I treat somebody with different conditions, you know, with pain involved, their pain can have drastic decrease very, very rapidly. Sometimes when I get off my examination table and their pain is, you know, 50% or even more gone. So that's the immediate, you know, response. And this, your immune system can come and start to break down the dysfunctional cells and remove them from the site. And then the second stage is a rebuilding of tissue. So that's going to take more time. This is why a person needs to be a little bit more patient when it comes to the rebuilding stage. Because building, you know, building of Rome doesn't take one day, right? You need to lay the bricks, you need to lay, you know, layer and layer to build the tissue that's, that's been damaged and that may take weeks to months. And then the very last stage, you know, after all this is done the last stage. You know, these stages overlap, right? They don't just do one after another. They can overlap and all happening kind of the same time, but some have a longer range. And the last stage is what's, what can be what we can call kind of a genetic modification or genetic repair type of effect. Because when the stem cells are in the body, how they communicate with the body a lot of times is through the exosomes. And what is included in the exosomes is a lot of growth factors, but also microrna. So these tiny little pieces of RNA carrying genetic information, they can go across the cell nucleus, so the membrane of the nucleus, and they can go in and interact with the DNA and they can change methylation patterns. They can actually make genetic changes, help repair the DNA, make them younger, make them functional, function better. So that will have much longer ranging benefit. And so you may not see it very clearly, but doesn't mean that they're not happening. They're making your DNA healthier. So that's a much longer, you know, that's months to, you know, even years of benefit. So that's kind of what I want to give people, a, you know, broad idea of just how interesting these cells work and, and what the healing process can, can be and, and you know, what you can expect. So don't, you don't expect miracle immediately because now you understand how the cells work. So I hope that's helpful and thank you for watching this and I hope you are as excited about this new branch of medicine as I am, because this is groundbreaking. This is the first time in human history that we're utilizing the intelligence that created us to help us heal. So I hope I see you very soon, that we get to do another episode soon. So see you next time.