How Stem Cells Work

are you being optimistic? I see? I think if this is good? I learned a lot about this topic. Yes, thank you for not blowing the big secret. That's right. We're talking about stem cells today. It's out there. Yep. You can't take it back. Nope. Um, did you know much about stem cells before? You researched the little bit? Keep up with the news a little bit on it, but I hadn't done a ton of research. It's really fascinating, Yeah,

it really is. What's funny is what I knew about it before, what I assumed, um, which is just this very primitive idea of like taking a cell and making it turn into some other cell that you want and then injecting it into the affected area. That's actually what stem cell therapy is. Yeah, that's the goal of it at this point pretty much yet one of them. Yeah, so basically it's the Caveman stream. That's what stem cells are.

Is that what it is? Yeah? I thought that was warm soup, warm soup alright, So after that, after warm soup was invented, they turned their attention to stem cells. Warm soup than cold beer stem cells. Yeah, that may have come first. You remember from the beer episode the idea that bread was created to make beer easier to make. Yeah, that's such an awesome idea. I love it. That's a T shirt right there. Yeah, it's a little plunk. I think we need to work on bread before beer. Oh

well there you go. Yeah yeah, he thought I was gonna put the whole thing. Yeah, it kind of keeps going onto the back of the shirt. Right. Oh, wow, you are in a weird mood today or inside? I know, I just like, I let even know what that was. Okay, let's let's take this seriously. Yes, so, um, there are plenty of diseases out there, chuck that affects cells like Parkinson's um. The neurons that produce dopamine, the neurotransmitter dopamine,

which helps control movements. UM, those cells die and as a result, you lack dopamine and as a result of that, you can't control your movements, and then you have the characteristic tremors of parkinson Um. Heart failure is apparently the result of well, your heart failing, but the heart failure comes from your heart cells dying off. It's all cellular death for the most part, well a lot of it is, right,

there's a lot of disease out there, type one die abetes. UM. I believe you're not producing insulin like you're supposed to the pancreas. Yeah, So the reason why cell death in the pancreas. So there's this whole idea that if you can just figure out how to reintroduce these cells, then the caveman's dream will be realized because you will have a healthy pancreas and therefore no more type one diabetes. You'll be producing UM dopamine again, no more Parkinson's and

possibly no more Alzheimer's either, yea, no more. A lot of stuff, yeah, And it all comes down to the fact that we are losing cells in a in an unnatural way, and there therefore, by replacing those cells, we could conceivably cure these diseases. Yeah, I guess we shouldn't say no more, but we should say reversible, you know, because you would still get Parkinson's, but then you'd be able to reverse the effects. We're not talking about eradicating.

Oh yeah, yeah, you know that's a that's a good point. Um, Yeah, we're talking about curing these things once you already have them.

Just saved us some pedantic emails. So the whole point to all this, the whole idea beneath it um was discovered in when some researchers figured out that there are cells in mice that are what are called undifferentiated, meaning they're not really any kind of cell, Like they don't carry oxygen in the blood, they're not capable of it, they're not capable of UM transmitting neurotransmitters, they don't they

didn't really seem to do anything. But then further and further research revealed like, oh my god, these cells can do anything. Yeah. They're like a little child, like what kind of cell do you want to be when you grow up? And those are stem cells, and then I think they finally isolated them in humans because the big problem with stem cells is they look and seem just like all the other cells that they're around until you figure out how to isolate them, which is something they're

actually still working on. That's right, and uh, they and we'll get to how they can mark these things, which is pretty neat in a bit. But um, there are not nearly as many stem cells as uh is one of the main differences. Yeah, depending on where you look. Yeah, for the adult and we'll get onto the different types as well, but for adult stem cells, it's about one for every one thousand regular cells. Yeah, and again, like in the blood, that's the case. In the bone you

might find one for every ten thousand. But the point is there's not nearly as many stem cells because you don't need as many. And the the analogy that I guess they made in this article is that stem cells are kind of like the body's repair kit. Yeah. The thing is is they don't necessarily do all the repairs that we need, Like you can still get Parkinson's and there's not a stem cell that automatically activates and cures your Parkinson's. If so then this we wouldn't be having

this conversation, that's right. So the goal of stem cell therapy used to figure out how to take these stem cells and make them do what you want them to do. Yeah, manipulating these cells to to turn into helpful cells. Regular cells can only replicate um to be another kind of

that cell, but stem cells are. They have different levels of what's called potency, which is an ability to change, ranging from a tote potent which can develop into anything anything, like it can turn into a car if it wants to. That's not true, it's like the Wonder Twins. Yeah, it can turn to anything, so long as it's water based, that's right. Uh. And then you have other levels of potency to pluripotent, multipotent, um. And we'll cover all this in detail as we go, because each one has a

different potency level, right. But I think that was descending order from uh capability, right, Like toted potent is anything, Yeah, pluripotent is almost anything. Then multipotent is a few things. Um. And we have uh, these stem cells, like we said, around the body in different places and and like you said, their their job is to basically hang out in there. Call it like their host organ or their host tissue. Yeah, like we're all in the liver. We're liver cells, right,

So you need a new you need a few liver cells. Here, I'm going to divide. I'm gonna divide into some more and then bam, no more cirrhosis, or at least it's staved off for another year. UM. With the bone marrow in particular, UM, there's a type of cell, or a type of stem cell called stromal stem cell, and that one UM creates all sorts of different types of blood cells. UM. Because your blood cells that's how they regenerate. Your stem cells they don't self regenerate, and they only last about

twenty eight days. Now, is that why you can use UM cells from bone marrow to treat other diseases like leukemia, other blood diseases? Exactly? And that is a procedure. It's actually stem cell therapy that predated our awareness that stem cells even existing. We just didn't call it a stem cell at the time. Yeah, it's a bone marrow transplant. That's what people still call it now we understand that what you're actually doing is transplanting that marrow that includes

some bone marrow stem cells. Yeah, into another person, and then those stromal stem cells will start to regenerate and help the person who has accepted this donation. That's right. So that was the that's that that happened even before we understood what stem cells were. But sin Um, all of this research has really been focused on, Okay, how can we make this a little more guided and laser focused rather than accidentally transplanting stem cells from one person's

bone marrow to another. And so what they started to investigate and found, Chuck, was that, uh, there's something called embryonic stem cells. And these were the first ones that were like this is awesome. Yeah, And like you said, they were isolated in humans and due to private funding, which is important designation because we'll get to all the controversies and federal funding coming up soon. But they are embryonic.

They're in the embryo, the fetus, or the umbilical cord blood, which is why a lot of times um mothers will save their umbilical cord or not themselves. They don't give it to them here you go, because that could come in handy later on um and it depends on what it's harvested. But they are the ones that are pluripotent, depending like I said, on when you get them. They can also very early on the the ultimate uh tote potent.

But that's um, that's super early. Yeah, you have to have a quick hand like this total day or so right old um. So those are the embryonic versions. Then you've got adult stem cells and um. Strangely a ault stem cells are found from infants on. So I think the adult refers to the actual stem cell rather than the person who has that type of stem cell. Yeah. I think it's like I guess, just sort of like post embryonic is the way I looked at it. Yeah, yeah,

that makes sense. It is multipotent, which means it can uh differentiate or change itself into a lot of different helpful things, but not as many as pluripotent. No. Um. And then lastly, in two thousand and six, some Japanese people figured out that you could English. Were they English too? Well, those two guys who won the Nobel Prize, it was Japanese one was they both deserve it because they figured out that you can take uh sell any kind of cell and make it regress back into a stem cell.

And that was huge because in part or mostly because of the big controversy around embryonic stem cells, which you said, we'll get into it in depth. Yeah, those are called induced pluripotent stem cells or I P S C S induced because they're inducing it in pluripotent because they revert back to uh, the very handy uh pluripotent stage. Uh. Those are the main three that's in general, and we'll talk about all of them a little more in that right after this. All right, so let's start with embryonic.

That seems like the logical place. Uh. If you listen to our in vitro fertilization podcast recently, you know all about, UM, how an embryo is formed. We have an egg fertilized by a sperm that divides becomes an embryo. It's basically that simple. I encourage you to go listen to that podcast,

though you'll learn all about all kinds of stuff. When you undergo IVF though, like we talked about in that episode, a lot of times you will have more embryo's not always um, but a lot of times you have more embryos than you're gonna use, and so you can freeze those and save them for later in case you get pregnant and that doesn't work out, um or it just becomes medical waste. You get pregnant, you're like, we don't

need those anymore. You can just discard them, or you can go with option three, which is to donate them uh to science to be used in stem cell cloning, therapeutic cloning. UM. The reason that they would want your embryos is because, like you said, there at some point total potent and definitely plural potent, very very versatile as far as stem cells go. UM, and you can it's very It's not easy. I don't think it's I don't

think that's the right word. But you can take a embryonic stem cell and culture it and let it divide into more and then culture those and culture those, and as long as they stay undifferentiated, you have a line of stem cells that can just keep replicating more and more stem cells. They're never going to turn into a certain kind of cell, that's right. So what you've just created is an embryonic stem cell line. The thing is, and this is what people have a problem with. To

harvest these things, you have to destroy the embryo. You have to you have to let it become a blasticist, which takes a couple of days, and by the time it becomes a blasticist, it's about a hundred cells wide or deep. There's and then inside this is the the embryonic stem cells. So basically you have to crack the blast eist open and then harvest the stem cells, and then there's nothing left to do with the the blasticist.

If you're a religious type and you believe that life begins at conception, then the problem is is you've just taken a life by destroying a blasticist, and uh, that's just one of the controversies. The therapeutic cloning is also controversial because that's when they merge a cell. You've got a patient who needs the therapy, and they merge that cell with a donor's egg and then remove the nucleus from that egg, replace it with the patients and it

basically is like their own. Now it's it's not likely to be rejected, which is a big problem. You're just basically using someone else's egg for its structural capabilities, and but the nucleus the thing that's saying like here, build this, go do this. It's it's going to look like you, not them. Yeah, but anytime you use that c word, uh, cloning. Yeah, well it's going to be controversy is going to ensue, of course indeed. But it's also a double controversy too,

because you have to do the same thing. You're still forming an embryo that you destroy once it gets the blasts of stage. It's just a freak of nature because you cloned it. It's called a double whammy. Right. So that was that's embryonic and you know, there's a lot of controversy around it. Um and we'll talk about that

a little more later. But there's another type of stem cell um that isn't nearly as controversial, if at all, and that's the adult stem cell which we mentioned, which doesn't mean you have only when you're an adult, but it's a type of stem cell that it's like the kind that hangs out in your bone marrow. It's it has a more of a specialized um job. Yeah, or it can become specialized, which is the key. Uh. And as you said, it hangs out and it can divide and help out the liver if it needs to, or

the pancreas if it needs to. And um, that's the main differentiate is that it's it's multipotent instead of pluripotent. It still has limits. UM, And it's basically again this is these are the ones that are your They're not there to create you the human for the first time. They're there to kind of keep you from wearing down too fast. Yeah, I wonder if I wonder if they're left over or if they're supposed to be there. I

know that sounds like a weird differentiation. I don't know, because I did see somewhere that um, they're still trying to figure out although this Japanese research may have figured it out, but they're trying to figure out why some types of stem cells, adults stem cells, we'll just sit there and just hang out for a very long time, and then all of a sudden they start to divide. So I don't know, maybe they are original cells. If they're just kind of hanging out doing nothing, why would

they age? I don't know. You know, it's weird. So we mentioned earlier that they one of the difficulties in working with stem cells, especially these adults them cells as they looked like other cells. So they have a really cool way of of marking them, or what they call lighting them up um or cells. UM. Every cell has a unique protein called a receptor on the surface and they bind these chemical messages. That's how cells talk to each other basically, And so they use these markers UM

to identify the adults them cells. They basically tag them, tag these chemical messages with fluorescent molecules and then once they put that fluorescent chemical in there, it lights up under a fluorescent light, so they make them kind of glow in the dark. Yeah, because that chemical message is now bound to the only type of cell that's it will bind to the stem cell. So then yeah, when you hit it with the black light, somebody should have won a Nobel price for that too, in my opinion,

black light. But it's the same as embryonic stem cells. UM. You can grow these in a petri dish. You can establish a new cell line, and they are extremely useful. And like you said there, they naturally say in the liver, create new liver cells. But they have been shown UM trans differentiation to undergo trans differentiation where they can be induced to do something slightly different. So like a liver stem cell can produce insulin, which is typically produced in

the pancreas, right, and they haven't. Um, they haven't quite figured that out yet, right, No, No, they do not know this. Like they know that stems somehow can be induced to do different things, they don't know how to do it yet. Yeah, this is all super new stuff for the most part, I mean, if you're talking since not a long time. They did recently figure out these uh hemo poet poietic Yeah, hemopoietic stem cell, which is a it's a type of blood stem cell that makes

all different kinds of blood cells. It's a very important one. And they found that by looking at zebra fish embryos, which are totally transparent. Um, they actually watched these things form and they just found out, like within the last couple of weeks that these require what they're calling a buddy cell to become the type of stem cell that forms blood. Right, So now they think that they're one

step closer to figuring out these hemopoieticum stem cells. They don't know what the buddy cell is or where it comes from, but then now they know that it needs a buddy so that these are kind of like these of the kind of piecemeal steps that we're making towards understanding stem cells. All right, and then we have our well maybe not final because you've already told us about the fourth, but the third uh type is what we

call the induced pluri potent stem cell. And um, that's the one that we mentioned was pioneered by Shinya Yamanaka. And Sir John almost said, Sir John Gruden. So, Sir John Gerdon, Well, who's John Gruden? And sounds so familis the NFL coach that looks like, oh yeah, Chucky Job's play. He didn't win a Nobel Prize though, but for their efforts in two thousand twelve, they did win a Nobel Prize.

And uh, basically, like you said, they found a way to induce these cells to return to their embryonic state, which is amazing. Yeah, it sounds like basically they're using epigenetics. Yeah, that's a dangerous word to say, too. Well, think of so like a cell. What they found is that cells change and become the way that they later become, like a liver cell or a bone cell or a neuron or something like that, because they all have the same

genetic code in them. But then certain gene sequences are either turned on or off in that cell and that changes or tells them or directs them to become what kind of cell they become. Right, what these guys have done is introduced what are called stem cell factors that go in and switch everything off to turn them back

into these plury potent stem cells. The thing that they haven't figured out how to do yet is to now activate them, to say, here's some new markers to change your your gene sequence and uh now become uh liver cell. Keep coming back to liver cells. I'm fixated on that. Um, that's that's the next step. Yeah. And the great thing about the I P s C is that it doesn't involve embryos, so that kind of skirched the ethical and

political side of things. Yeah, because you can take a skin cell and again, these guys are having a one percent success rate, which is not bad. No, but if you if if this, uh this other researcher has figured out how to make them at that's even better. Yeah. And these are it's such a new um, a new process with the I s PC is they need to do research to see how effective they are in treatment. Uh, if they are identical to embryonics themselves, or if they

just behave a lot like them. Um, So the proof in the pudding will becoming hopefully in recent and uh in the coming years exactly, not recent years, in coming years, in coming years. So Chuck, let's talk about how they hope to actually use stem cells in the future once they have mastered these things after this. Okay, So using the stem cells is very important. You can create all these cell lines and they can live a very great life in a petri dish. But unless we're saving lives

and reversing disease, um, what good are they? Well, so far no good. But hopefully what they're what they're thinking of, is they'll be able to use these things for say like drug drug trials. Yeah, that's huge, because right now what you have to do is test something on an animal and then think, all right, well, if it does this in a mouse, let's try and figure out how it might work in a human instead of just testing

it directly on human cells. Apparently the steps you followed are mouse, monkey, human, unless there's in a bowl outbreak and then you just go straight to human. Get the FDA to pass it. Right. So, if you're if you're creating like a heart drug or something, and you can induce some um, stem cell else to become heart cells, heart tissue, and then test the drug out on this. You're basically just running human trials right there. Yeah, you're

skipping steps, you're saving time, you're saving money, cutting corners. Ah, yeah, that is a negative. So that's one that is one idea behind a good way to use these stem cells. Let them stop living their life of leisure and start contributing for once. Yeah, and forget the drug trials. Maybe they can actually, like you said earlier, I think of the beginning, just inject it right into the heart, let's say, to repair damage tissue. And they they've actually had some

success with this and mice. Again, our understanding of some stem cells and what they're doing is kind of primitive. But they took mice with bad tickers and they injected them with heart stem cells, and um, all of a sudden, the mice had like super hearts. But they don't know if these stem cells went in and regrew heart like, cardiac muscle tissue, new blood vessels. They're not sure why. They just know that the mice the arts. Yeah, yeah,

we're better. Uh. And as they go along testing all these things, one of the things they have to get around. One of the hurdles is um rejection, like uh, bone marrow transplant, any kind of transplant on the body. Really there's a chance that your body will reject it and say this is a foreign invader, maybe going and attack it and kill it. Um. But one of the cool things about the I P s C Is since it comes from your own body, has a probably a greater

chance of not being rejected. Yeah. Same with using adult stem cells. They're gonna take them from you and use them on yourself. So that's very promising as well. So, Chuck, we've been kind of skirting around this issue a little bit, but um, we we may mention that embryonic stem cells do represent a very controversial piece of scientific research because to some they represent the destruction of life. Yeah, and

it it all kind of got started with the Clinton administration. UM. The National Institute of Health Human Embryo Research Panel advised Billy Boy to authorize funding for research on leftover embryos from IVF treatments that we mentioned, uh, and to create new embryos um from scratch for research purposes. And he said, the first one sounds good, but I don't know about that second one. Let me ask new gingrids. Can you say that, like, like Clinton, let me ask new Gingrich.

I thought you were asking me to do a new Gingrich. I was like, I have no idea how to do. He was pretty Uh he didn't have like a very remarkable accent, especially not for being in Georgian. Yeah, that's true. Um. So that was and um, like we said, in is when things really got rolling because of private funding. But by then Congress had already put the brakes on it. Yep, because in n there was a writer on another bill called the Dickey Wicker Amendment from J. Dickey and Roger Wicker.

Doesn't that sound like a British amendment? It does? The Wicker um probably because of Sticky Wicket in cricket, right right. Uh. And they proposed banning federal funding for any research in which you destroy the embryo. Yeah, so I mean, like it wasn't specifically limited to stem cell research, but like we said, to get to the stem cells, you have to crack open the blast asist, which destroys the embryo, which in effect put the freeze on creating any new

stem cell lines pretty much. And they've renewed it every year since then. Um. But like anything in the US government, there's all sorts of ways to get around it, and one is the executive order. Right. And Bush came in and he issued his own executive orders, right, which kind

of strengthened the existing rules on embryonic research. Yeah, and that's the one where he said you could use federal funds only on those established lines, either the nineteen or the twenty two, uh, depending on guess where you're getting your info. And um, it prevented basically any funding federal funding for creating these new lines. Um. So, like you

said earlier, I think they were grandfathered in, right. And and the problem with that is, I mean, these stem cell lines can produce millions of new stem cells and within a matter of months, but you need even more for decent research. So there was in the United States at least a lot of there was a huge freezing effect on stem cell research. It just wasn't nearly as widespread as it could be, at least if you wanted

federal funding for your lab. Yeah. Um. And so under Bush, the I guess there was just there was still this huge national debate about it, and the Bush administration sided with the pro life lobby and said no, you guys can just do this, but how about this, I mean to issue an executive order encouraging you to go figure out a way to start new stem cell lines without destroying embryos. Go, and I guess you can kind of say. Well, then after that there was the induced plur potent stem cells.

I think they were probably already working on those. I don't know if it was a tribute to Bush's challenge or anything like that, but it did come after that. Yeah, So that was all in two thousand one ish, and then UH in two thousand five. By the time that came around, UM, the House and the Senate both UM, even modern Republicans started to kind of get on board a little bit more, say, Hey, maybe we need to broaden this thing a little bit because it's super promising.

So let's introduce a couple of a couple of acts, the Stem Cell Research Enhancement Act of two thousand five, and that would have allowed federal funding of research on UH these new lines, not those grandfathered in only from the discarded embryos um from fertility treatments. The House passed it to UH. Senate passed it six three to thirty seven, and Bush vetoed that. He said he was gonna veto it. It's one of those deals. He's like, go ahead and vote,

I'm gonna veto it. They voted, he vetoed it. Uh, they did not. They tried to override the veto the House did, but they failed to. And then the stem Cell Research Enhancement Act of two thousand seven was similar to the original and two thousand five that passed the Senate and House as well, and uh, Bush vetoed that one as well. Okay, so that was the climate that the Obama comes in. Yeah, and and uh again he you know, Bush wasn't saying I hate stem cell research.

It's it's stupid and I want people to die. He was saying, we should only do it in certain ways that don't violate, Uh, what a lot of people feel like are you know, life begins that, you know that very first day? Right, So Obama comes in and says, forget that, if you have your nineteen or twenty two stem cell lines, you can get federal funding for working on those lines. Everybody, that's cool, And how about some new lines? If somebody is going to discard embryos from

in vitro fertilization, and they want to donate them. And these people are aware that these things are going to be used for medical research. Then you can create new stem cell lines using federal funding and that you're not paying those people. That was the final step. Yeah. Um. And so a couple of ironically, a couple of stem cell researchers sued um to get these rules stopped from

being put into place. Um, and they actually won. Uh. Their case was overturned on appeals I believe, who basically also said, you know what this uh, what is it? The Dicky Whate Amendment, the sticky wick, the wick, the Dicky Wicker Amendment is overly broad, and so we're gonna limit this and everything. Obama just said in his an executive order, just go ahead, and we're gonna go forward

with those rules. So that's the current state of affairs right now, is an appeals court interpreted this legislative act is overly broad, and we're operating under an executive order that's allowing federal funding for embryonic stem cell research to continue. Nothing's really changed as far as the national conversation goes. It feels like it's just died down. A bit as far as the volume goes. And um, they've never banned research.

It's just a matter of restrictions on federal funding and use. Um. Yeah, well they also didn't ban research on gun violence. They just stopped funding that too. That's right, remember that I do. Yeah, you got anything else? I got nothing else? Okay, Well that's stem cells at least as far as um it goes in August two thousand fourteen. Yeah, two thousand fourteen. I'm sure that in five years it's gonna be a

whole new world. Yeah, you never know, we might see the end of Parkinson's and MS and Alzheimer's and it just inject some new cells in there. Uh. If you want to more about stem cells, you can type those words into the search part how stuff works dot com. And uh, since I said search parts, time for a listener mail. I'm gonna call this banana flavoring. Um. I can't remember which podcast it was, Plato, but um I said that I didn't never like banana flavoring and stuff,

but I like bananas, and you were like what. We got quite a few emails explaining this, and I'm super happy because I get it now. Um, and this is from Elliott. Um, you guys seem to be unaware of why the flavor is different. Currently, we most commonly enjoy what is called the Cavendish banana. Have you ever heard of that? Yeah? I did it. Don't be dumb on banana clone? Oh you did? Well? How about that? Uh? There are the long yellow bananas people like to have

on their Sundays. Before the nineteen sixties, and most commonly purchased banana was the the big Mic or the gross Mikael. I guess it came from Germany. It's definitely gross means big. Uh. There are the bananas. These are the bananas that banana candy is based on. Um. After Panama disease, which was a fungus, wiped out large amounts of big mics, most markets switched over to the Cavendish. The worry now is that the Cavendish may be affected in the same way soon.

UM Mono cultures aren't the best plan, apparently, So essentially, the bananas that we eat now that we know and love, the banana flavoring that they use is not based on those bananas, and that's why it taste weird. Um. That's pretty interesting and a lot of people send this in so I tend to believe it because if like four people say something, yeah, it's definitely right. Uh. And here's

an extra factory, he says. Cherry flavor is based on Maraschino cherries, which is which are in turn flavored with almond extracts. So cherry flavored candy is somewhat almond flavored. And thanks for the great show. I look forward to every episode. And that is from Elliott. Thanks Elliott, good

stuff there, Cavendish Big Mica had no idea. Yeah, and like bananas are all a sexual, so every banana that you've ever had is an exact clone of its pro janitor crazy and that I'm gonna watch that Don't Be Dumb episode. Let's do it right now. Yeah, Okay, if you want to check out Don't Be Dumb, you can go to our website, but first you should get in touch with us via s Y s K podcast on Twitter, at our Facebook dot com slash stuff you Should Know page.

You can email us if you want and just send it to stuff podcast at how stuff first dot com um and you can check out all of our videos, all of our cool stuff, and just generally hang out and be our friends at our home on the web, the clubhouse known as stuff you dot com. For more on this and thousands of other topics, is It How stuff Works dot com.