AASCP Lecture: Best Tissue Source of MSC's Part 1 - Joy Kong, M.D.

Every source, they work. So but some sources, cells from some sources might work this well, but what if from another source works this well? People are paying a lot of money to get these treatments. So should I give them a cell that would produce this kind of results or that kind of result? So that's a matter of degree. So I want to show you the scientific data of what's out there. You know, let's talk about the nitty gritty of these cells. So, oh, the disclos. I'm in Los Angeles, so I treat a lot of patients in my own clinic. I'm also the founder and medical director of Charobiologics and also medical advisor for Lennox usa. So those are my disclosures. So let's talk about these. So first of all, blocking anybody, what are mics? So what's interesting is in about 20, 25 years ago, people still believe that the only stem cells in the body were hematopoietic stem cells. But in the early that's when MSCs were finally found and named. They represent the class of cells that has in vitro capacity to form mesenchymal mesodermal tissues, lung cartilage and fat. And they've been given many names. They all stand for msc, but there's marrow stromal cells. Initially they were discovered in bone marrow multipotent stromal cells, mesodermal stem cells, mesentery stromal cells. So all these names. The discoverer of the MSC or the father of MSC, Dr. Arnold Kaplan. I'm sure everybody has heard him. So he has been very adamant in trying to get the word out to prohibit people from calling these stem cells. I think he admitted that when he first called them stem cells he was trying to create a little bit of controversy. So I think he's still trying to create a little bit of controversy. Now he wants to pre them to be named as medicinal signaling cells because really that's what these cells, that's the main function they have in their body. And that's not so much that they are going to differentiate and become all these other cells, although they can. And so that's where I don't agree with him because I do think they are stem cells. But what he's trying to do is to try to prevent this mis conception when it comes to patients, because we're telling patients we're giving you stem cells. So people are somehow having this, you know, this mythical notion that these are going to be the cells that transform into my own tissue that's going to replace my tissue but really the main function is the paracrine effect is how these cells, what they're going to promote when they're in your body promoting regeneration and a whole slew of other effects that I'll talk about. So these cells are derived from parasites so hovering right around blood vessels and they are all over your body, in all your tissues. So any tissue that's vascularized, you have these mesenchymal stem cells. So MSCs and in each tissue these MSCs actually have contact with all the local stem cells. So they are actually acting like a conductor, like an orchestrator up regeneration. So they're able to sense cells, they are tissue specific because each tissue, the mesenchymal stem cells are different. Just because they're all mesenchymal stem cells doesn't make them all the same. So they all have a little bit of different characteristics and they're able to talk with the local stem cells, speak their language. And so why are we talking about msc? So this is the important part because of all these things that make them important. First of all there's regenerative properties. So these cells are able to hone in to areas of inflammation and injury, actually secrete these therapeutic factors. So they secrete growth factors, chemokines and they promote cell proliferation, differentiation and angiogenesis. So that's the promoting regeneration part. And then they're very anti inflammatory. So these cells can secrete these anti inflammatory cytokines in response to inflammation. So that's a huge part of their effect. And then they also have immune modulatory effects because they let you say in autoimmune conditions they're able to promote this transition from the T1 dominant system into a T2 dominant. So things in the body are more anti inflammatory. So healing and repair can occur. Because a lot of modern diseases we all know is the is the flaming inflammation that's not calming down. So we're not really repairing. Besides the fact that we do have less and less stem cells and we have more and more toxic buildup and then anti apoptotic. So we're talking about stroke. Other presenters. So when some cells, let's say stroke area, the central stroke area, cells are dying and then they secrete these chemicals and they're spilling out their gut. So all the neighboring cells are receiving the message saying it's time to die too. So this programmed self death. So these mesenchymal stem cells are able to stop that process saying hey no, you don't have to die. So either hypoxia, chemical, mechanical Kind of damage radiation. And then they also have antimicrobial properties. Very interesting. So they've been shown to have effect against acute and chronic infections. So they secrete antibiotic proteins. How convenient. And they've been shown to be effective against bacteria, virus and some protozoan organisms. And okay, so MSCs are everywhere, all vascularized tissues. So are they equivalent? Are they all the same? So let's look at some of the popular ways of exchange. Tracking MSC1 is bone marrow aspiration, right? So that's how things were started initially. That's earliest stem cell transplant is through bone marrow. So cells are extracted from the, from the iliac crest. And so the bone marrow has about 0.001 to 0.01% of MSCs. That's the stat. And then we have fat derived MSCs. So mini liposuctions can be performed. And within the fat tissue, which is very well vascularized tissue, there's a much higher percentage of MSC. About 3 to 10% are MSCs. So these can also be obtained. And you know, it has become very popular and of course in the US is not allowed to use enzymes. You know, the FDA doesn't allow the use of enzymes or expansion. So the number, you know, it's not quite as high as, you know, if you do it in the US and then the next one. So this is just a little bit more detail you guys probably all know about how the SPF is obtained, where the, the aspirate is spun down and then you get the cells and then you get secretomes and they can exert therapeutic factors. So the most important question to me is, does age matter? So you're obtaining cells from an adult, you know, either a 25 year old or a 65 year old. Does the age matter? So what we know is that because these MSCs do persevere in your body for a lifetime, they do accumulate certain cellular damages they are susceptible to. So these damages can cause cell death, senescence, loss of regenerative function, or even neoplastic transformation. Whereas if you look at neonatal stem cells, MSCs, they're spared from all this, all these pro aging factors. So it's not just me talking about, you know, that age matters. So let's look at some evidence. So a lot of research has been done. First of all. So this study, age, the first one. Age, age. Adipose derived mics are significantly compromised in their ability to support vascular network formation. So they're not able to rescue a age associated impairment in cutaneous wound healing. So when we cut ourselves when I when you use adipose derived stem cells, especially from older person, they're not as effective. And bone marrow derived stem cells, the second one when it compared to younger MSCs they have less myogenic potential and engraftment properties. And then bone marrow derived stem cells also exhibit age related decline in all kinds of responses, inflammatory response and they also express express less cytokines than chemokines that are important for the MSE's migration to the site and their activation and their immune modulating properties. So more, you know, more research. So genes related to senescence are increased in adipose derived stem cells with age. So the older you are, the more senescence genes are expressed. And aging also affects availability of certain expression, certain markers and their angiogenic properties. So the ability to form new blood vessels is impaired. The increase also when cells age, they've shown in bone marrow stem cells, the older they are, the more they accumulate reactive oxygen species we all know that cause a lot of cell damage, DNA damage and not only they have increased level of these reactive oxygen species, they're also more susceptible to their damage. So they're more sensitive to the microenvironment that's produced by these reactive oxygen species. So basically they're kind of weakened, they're a little bit easier to damage and a little bit more so young stems of mesenchymal stem cell from age 1 to 5 when they compared in cardiac repair after MI, comparing to transplanting older MSC.