IRA FLATOW, HOST:
This is SCIENCE FRIDAY, I'm Ira Flatow. Every once in a while there is a study that gives scientists a new way to look at an old problem, and a group of researchers say their study in Nature Communications this week does just that.
For decades, scientists have thought that heart disease is caused by smooth muscle cells that line the walls of blood vessels. The belief is that when blood vessels are damaged by LDL or that bad cholesterol, the smooth muscle cells are triggered to proliferate. So they build up scar tissue that makes the vessel both narrow and hardened.
And these changes can restrict blood flow and may cause heart attack or stroke, a leading cause of death in America. But a team led by scientists at UC Berkeley says that they have uncovered the real culprit behind clogged arteries, and it's not just smooth muscle cells, as previously thought, but stem cells, a finding if corroborated that could lead to a new direction for future treatment of heart disease.
Dr. Jill Helms is a professor in the Department of Surgery at Stanford School of Medicine. She is co-author of the study and joins us from Stanford. Welcome to SCIENCE FRIDAY.
DR. JILL HELMS: Well, my pleasure to be here, Ira. I want to start out by telling you that you and SCIENCE FRIDAY have a great fan base here at Stanford.
FLATOW: Well, that's very good to hear. Thank you very much.
HELMS: You're welcome.
FLATOW: And we're enjoying the work that you're helping us broadcast about, which is what I want to talk today about. This is really interesting. Before the study, we thought that clogged arteries are clogged by how? And what have you done to change that view?
HELMS: Well, I think that the prevailing idea was that clogged arteries are caused by a group of cells that exist around a blood vessel, and they begin to grow or proliferate, as you had mentioned. And I guess it's sort of like a pair of Spanx that goes out of control.
You know, normally the cells around the vessel hold it in a snug manner, but when the cells around the blood vessel grow too much, then they narrow the lumina(ph), the diameter of the vessel. And I think that's where the big - of course we understood which cells were responsible, or I should say we thought we knew, and that's where Song Lee(ph) and his students made a really critical insight.
They saw that instead of this - just smooth muscle cells, there was actually two populations, and the second was a stem cell-like population. This appears to be the cells that caused the trouble.
FLATOW: So the stem cells start to proliferate and create smooth muscle cells on the wall of the artery?
HELMS: They create all sorts of things - excuse me. As a consequence of their being stem cells, of course they're capable of differentiating into lots of different cell types, and that's what Song showed. He showed that they could differentiate into fat-producing adipocytes, bone-producing osteoblasts, even differentiate into neural cells.
And that's where he made a key discovery, I think, in that understanding that these were stem cells.
FLATOW: And so these cells, would they be lining the artery walls in all different forms, as...
HELMS: That's right.
FLATOW: You know, that's why there's calcium deposits there sometimes perhaps, because it may be bone?
HELMS: That's right. That's - the capability of these cells to differentiate into bone-producing cells is, of course, associated with vascular diseases. And so I guess where I came in was that we were working on these areas. Even though he works just across the Bay from me - I met him at a meeting in Japan that was sponsored by the California Institute for Regenerative Medicine, or CIRM, and they fund a lot of stem cell research in California.
FLATOW: And so what did you do to prove this, to show it in operation?
HELMS: So the important part was to be able to demonstrate that these cells really were stem cells, and he had an idea that they were derived from a population called the neural crest. And that's the area that I work in. Neural crest cells are an embryonic population of cells that have the same ability to make fat, bone, cartilage, nerve, and as a consequence of the similarities between the two cell types, we found that indeed the cells that exist around the vessels, these stem cell-like, the stem cells that exist around the vessels, look like neural crest cells.
This gives us a real handle on what their behavior is and what might regulate them in disease states.
FLATOW: Well, if you see them there, could you actually show them in action clogging the arteries up?
HELMS: Well, in action is a difficult thing because that requires some kind of dynamic visualization of the process. And, you know, it's a slow process, getting our arteries hardened. But what you can do is create the disease in animals and then follow, using genetic strategies, follow the fates of the cells so that we can sort of indelibly label the cells, when they're still stem cells, and then follow where they go in the disease state.
And using that kind of approach, we are able to show that they are indeed stem cells.
FLATOW: So you can label them with a dye or something and see where they proliferate, and if they line the arteries, there they are, and they're creating stuff.
HELMS: Yes, very close to that. It's a genetic strategy, so it's not a dye, actually, but a gene that makes a protein that can be detected by a dye reaction.
FLATOW: 1-800-989-8255, talking with Dr. Jill Helms, saying that - if I may summarize this, and correct me if I'm wrong - is that stem cells are at the root of hardening of the arteries. That simple.
HELMS: Yes, yes.
FLATOW: Wow, and...
HELMS: I will say that one of the big opportunities this presents is that when you know the cause of a disease, then you can start thinking about ways to target that disease process. And this is where our collaboration is going. And Song has developed a number of techniques to rapidly screen drugs that will specifically target these cells and not the cells that line a blood vessel, called the endothelial cells, so sparing one cell and targeting the other for therapy.
FLATOW: But stem cells are all over the body, are they not? Could you target the wrong kinds of stem cells if you just...
HELMS: Absolutely, that's certainly a concern. And so it's lucky that they are spatially restricted, so we know exactly where they reside. If one were to think about targeting, you'd have to take into account that sort of spatial component.
FLATOW: 1-800-989-8255 is our number. Now, with the discovery that stem cells cause heart disease and hardening of the arteries, would they not be good candidates for other things that go wrong?
HELMS: Exactly. Right. So instead of now - now, of course, the therapies for treating hardening of the arteries or narrowing of the blood vessels are mostly procedures that physically widen the inside of the blood vessel or else replace the damaged by grafting.
FLATOW: Like a stent or something like that.
HELMS: That's exactly right. So there may be an opportunity here to think about regenerating the correctly formed kind of stem cells that reside around the blood vessels.
FLATOW: And would they - would they be able to replace the damaged ones, if they regenerate?
HELMS: Well, of course that's still in the future, but I think that that's definitely a feasible option.
FLATOW: And as far as things that are not concerned with the heart, other illnesses, could stem cells - let me just throw out a few illnesses. Could they be involved in arthritis or something else like that, and we don't know that yet, you know?
HELMS: That's right. We don't know it about arthritis, but I will tell you that cancer is certainly a disease that looks very much like a stem cell gone out of control. And so if we understand what normally regulates a stem cell's behavior, then we gain some crucial insights into what regulates maybe a cancer cell's behavior.
It's that kind of approach that I think that CIRM is largely funding initiatives to try to target human diseases, the big ones, and the ones that make us all sort of quake in our shoes, and attempt to come up with new therapies.
FLATOW: Yeah, a couple of questions come to mind, is why - and you'd want to know why only in some people do the stem cells get activated to do...
HELMS: That's right.
FLATOW: Right? What's the vulnerability there?
HELMS: What is - and we know some of the things, right? We know some things that activate stem cells like repeated injuries, things like smoking. Inhalation injury triggers activation of cells, stem cells around the lumen of the bronchials. Or drinking to excess, you know, damages the liver, activating stem cells there that then go out of control.
So clearly understanding how injuries, some environmental influences, and of course the genetics of each individual, how those may play into activating these stem cells and leading to disease.
FLATOW: Bridget(ph) in Raleigh, North Carolina wants to join us. Welcome, Bridget.
FLATOW: Hi there.
BRIDGET: I just had a quick question. When you refer to hardening of the arteries, are you referring to arteriosclerosis, arthrosclerosis, or both in this context?
HELMS: I think both is a fair - certainly arthrosclerosis.
FLATOW: One is - tell us the difference, quickly, between them, Dr. Helms.
HELMS: Well, you know, this is getting outside of my area of expertise because I'm not a cardiologist.
FLATOW: Well, there's a simple - I mean, one - I'll just take a shot at it.
FLATOW: One is thickening of the - one is narrowing of the passageway in the arteries, and the other is actually hardening of the arteries, and those are two different things. Would I - would you go that far with me?
HELMS: Yes. I'd go that far, I guess, because I'm thinking about the contribution of these cells...
HELMS: ...to disease. I would say it's more closely linked to atherosclerosis.
FLATOW: And that is the narrowing of the arteries.
FLATOW: Yeah. And what do the stem cells normally do when they're there and they're not doing, you know, turning into - doing this bad thing? What do they normally do...
FLATOW: ...in the body there?
HELMS: You know, we have no idea.
FLATOW: We don't?
HELMS: We have no idea what their normal role is sitting there. And then that begs the question, how did they get there? Where did they come from? Were they always there from the beginning of our embryonic life, or did they migrate there in response to a stimulus? We don't know.
FLATOW: Wow. But we knew they were there for how long? When did we discover that?
HELMS: Oh, only recently.
HELMS: This is - I think this is probably the biggest discovery that comes out of this work from Song Li and his colleagues and that - in which I participated.
FLATOW: So wouldn't you think if there are just stem cells in the arteries, and they're - and we know they're - we know that they float around in the bloodstream that there are stem cells everywhere else, in other tissue, in (unintelligible).
HELMS: Well, stem cells don't float around much in the bloodstream, unless they're blood stem cells. And most of the blood stem cells are actually in the marrow. So they don't float around. Cells really like to attach to things. You know, that's how they grow, and that's how they - they have to - stem cells have to be close to something we call the niche, which is a physical location that provides growth signals to keep the stem cells in a quiescent state. So how did they get there? You know, they didn't just crawl through the body. Something had to have caused them to be there, maybe from the beginning of our development...
HELMS: ...or maybe not.
FLATOW: Now, your work involves laboratory animals.
HELMS: That's correct.
FLATOW: When will this be moved over to humans, to look at humans in these (unintelligible)?
HELMS: Well, I think that's one of the, you know, most basic scientists that work in stem cells and in the area of stem cell are trying as hard as possible to move this into translational therapies, things that can be used in humans. And, of course, CIRM, our funding institution, is very adamant about this being the trajectory. So, you know, I'll be taking a stab at it about five to seven years. I think that the ability to rapidly screen existing drugs for their ability to target this cell population is why we think that it might have a shorter course to getting into humans.
FLATOW: Let's go to Gina(ph) in Barrington, New Jersey. Hi, Gina.
GINA: Hi. How are you?
FLATOW: Hi there.
GINA: Yes. I find this very interesting. I actually used to do a little bit of research myself in atherosclerosis and diabetes. And we kind of looked at things from a higher - kind of a higher outlook. And I wonder what your thoughts were on, with the stem cells actually congregating and proliferating there, why would they actually be going there, and would you believe this to be part of this theory that inflammation in of itself, that atherosclerosis is an inflammatory disease, and that is really the root cause is actually lifestyle, eating behaviors and lack of activity in general that's causing our body to react in an inflammatory manner?
FLATOW: All right, Gina, thanks.
HELMS: Wow, that's a great question. What causes them to get to the site of injury or where the injury happens and what activates them if they're already there? And inflammation, as the caller pointed out, is a key feature of a lot of kinds of diseases, including this one. And so it may well play a role. The difficulty is that most mouse models or animal models that try to sort of test the contributions of the immune system, we can only knock out certain parts of the immune system. It's very hard to collectively say it's due to an immune response or an inflammatory response. But it's clearly on the shortlist of the causes that lead to the activation of these cells.
FLATOW: You know, whenever you come up with a sort of paradigm-shifting idea, like this seems to be, there's great resistance to accept it.
HELMS: Oh, yeah.
HELMS: Yeah. But sometimes, I think scientists recognize - it's sort of the aha, right? Oh, it's like, I guess, yeah, if you look hard, sure enough, there they are. So I think it is - there is resistance oftentimes, but there can be moments where there's great clarity. And I think Song's work certainly falls within that category.
FLATOW: Will it have to be repeated by others to confirm what (unintelligible)?
HELMS: You know, that is exactly how science is done - show again. It's called research, not search. So, I guess, that means that, yes, absolutely. We need to confirm it in other animals too, and now, the group is getting human cells from diseased arteries, coronary arteries, to see if this paradigm still holds true in humans. Of course, that's our target.
FLATOW: Yeah. Is it the same kind of stem cells in humans as in these lab animals?
HELMS: Yes, they appear to be very, very similar. There's pretty much an indistinguishable - if there are differences, we haven't found them yet...
FLATOW: Let me get a...
HELMS: ...so that makes...
HELMS: ...that makes mice a pretty good model.
FLATOW: Let me get a quick question here from Andrew in Morristown, Tennessee. Hi, Andrew.
ANDREW: Hi. How are you all today?
FLATOW: Hi there.
ANDREW: My question is - well, first, I have a comment. I've believed for a number of years that stem cells are going to really just be a great thing in the medical, like, community. I think that...
FLATOW: Andrew, if you have a question you got to get in soon because we're running of out of time.
ANDREW: OK. Sorry. Do you think that this new study will hurt stem cell research?
HELMS: Absolutely not. The more we know about how stem cells behave, the more we can control that behavior, whether it's to repress them or to activate them. So it's all about getting the instruction manual for how a stem cell works. That's our goal. And with that information in hand, we can attack a lot of diseases.
FLATOW: Were these embryonic stem cells or were they other stem - kinds of stem cells?
HELMS: These were adult stem cells. These are all adult stem cells.
FLATOW: Dr. Helms, thank you for taking time to be with us today.
HELMS: My pleasure.
FLATOW: And thanks for you all folks listening out there at the - in your school. Dr. Jill Helms is professor in the Department of Surgery at Stanford School of Medicine and co-author of the study in Nature Communications. We're going to take a break. And after we come back from the break, Alan Alda is back with the winner of his flame challenge. We'll have the winner on. We'll be talking with Alan Alda and the winner, and Flora is going to join us because it's also our Video Pick of the Week. If you haven't seen this video yet, it's amazing, go to our website at sciencefriday.com, get yourself a preview of the video before we go to it after the break, and we will talk about the flame challenge of Alan Alda after the break. So stay with us. We'll be right back.
FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY from NPR. Transcript provided by NPR, Copyright NPR.