Scientists Derive New Type of Embryonic Stem Cell Scientists have derived a new type of mouse stem cell. They say it is a closer match to human cells than the stem cells currently available. Guests discuss what the new discovery could mean for the use of embryonic stem cells in medicine.
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Scientists Derive New Type of Embryonic Stem Cell

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Scientists Derive New Type of Embryonic Stem Cell

Scientists Derive New Type of Embryonic Stem Cell

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You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.

And we've sort of gotten into some interesting discussion in sort of a theme of basic research, implications of basic research this hour.

And up next, I want to talk about another development in basic research that will have applications beyond just the basic research. And that is a new and better embryonic stem cell, and a pair of reports in this week's issue of the journal Nature.

Two researchers announced the discovery of a new type of mouse embryonic stem cell. We're not talking about a human embryonic stem cell here. We're talking about a research tool, a new mouse embryonic stem cell. The researchers say it's important because it's a closer match to human cells than mouse embryonic stem cells available now, something of a missing link, if you will, between human cells and mouse cells. And that's important, they say, because it's a better tool for understanding human stem cells and how they might be used in medicine.

So for the rest of the hour, we're going to check in on the field of stem cell research, talk about what this and other new research advances mean for the clinical use of these cells and for getting a better understanding of the basic biology of the cells that give rise to all other types of cells.

So if you'd like to join in, our number is 1-800-989-8255, 1-800-989-TALK.

Ron McKay is the lead author of one of the Nature papers. He is a stem cell scientist at the National Institute of Neurological Disorders and Stroke at NIH in Bethesda. He joins us by phone. Welcome to the program, Dr. McKay.

Dr. RON McKAY (Stem Cell Scientist, National Institute of Neurological Disorders and Stroke): Thank you.

FLATOW: Let's talk about these new stem cells and what they are. They're embryonic stem cells and they're different than ones you've been using before.

Dr. McKAY: They are. They are from the mouse, as you say, and the - probably, the most interesting way of, for people to think about this is that we want to know where we come from, where all the cell types of the body are generated. And there's a lot of interest in the type of cell that's called pluripotent, which means that it makes all the cells of the body. And up until now, there's really only two completely clear pluripotent cells, it's the mouse embryonic stem cell, discovered about 20 or 30 years ago, and then less than 10 years ago, scientists reported a human embryonic stem cell, which was - could also make all the cells of the body.

And - but the two cells were different. The mouse cell and the human cell were really quite different. And what we and the group in Oxford - we collaborated with the group on Oxford - and independently, a group in Cambridge in the U.K., what we're all reporting is that actually there's a new kind of mouse cell, which is very similar to the human cell. So now we begin to understand better that there's two different kinds of pluripotent state.

FLATOW: When you say there's a new one, does that mean that's newly discovered? You just missed finding it or it's really a new cell? I can't imagine it's something new.

Dr. McKAY: No, it's newly discovered.

FLATOW: Newly discovered.

Dr. McKAY: Yeah. And the reason - I mean, it's interesting to ask why did we miss it?


Dr. McKAY: And the answer is that this cell exists for a very short window of development, and that - and the way we found it was by taking the mouse embryo just to the point where its implants. And that's a very difficult stage to study for most people. But our collaborators were particularly gifted in early mouse embryology. So we isolated these cells. And once you get the hang of it, these cells are easy to grow. And that - but as I say they're different from the classic mouse cell, and they are similar in some crucial ways to the human cells that have been discussed so widely.

FLATOW: Well, let's talk about what are the advantages. What crucial differences are there and why we like them so much?

Dr. McKAY: So - I mean, one simple way of seeing why they're so interesting is because they're the sort of - they are the cell that most immediately turns into the cells that you might be sort of more, sort of, obviously interested in, like heart cells or brain cells. So these are - this cell type, this new cell type is a cell that immediately does that.

Another reason why they're interesting is that the growth conditions, the mechanisms, which are controlling their growth, are different from the earlier mouse ESL state, and they're very similar to the growth conditions, which are controlling human cells, and actually they're quite similar in general to growth conditions, which are controlling stem cells. So these mechanisms of growth control, for example, have - may have a lot to teach us about the mechanisms of cancer.

FLATOW: Mm-hmm. Why are they being called the missing link?

Dr. McKAY: Because they represent this, sort of, step between this earlier cell that was - you know why, I think, in a way, it's sort of like, partly, it's sort of, it just sort of sounds good. But partly…

FLATOW: That helps sometimes.

Dr. McKAY: Sorry?

FLATOW: Yeah, that helps.

Dr. McKAY: It helps a lot. Sure. But, I mean, but partly, it's also that it's sort of - it's making things clear, right? Because it links this sort of mysterious thing, this embryonic stem cell, to all the cells of the body. It sort of - and it's a sort of way of just simply, sort of in a simple way, representing the advance in our thinking.

FLATOW: Mm-hmm. Now, what do these new cells, the newly discovered cells, as you say, which would be more properly to described.

Dr. McKAY: Yeah.

FLATOW: What do they allow us to do specifically, and what things can we study now that we couldn't study before?

Dr. McKAY: Well, let's go back to this missing link idea as a methapor. Let's say we're in New York City. And somebody simply tells you, you've got to walk to Santa Fe, right? If those are the only instructions that you get, you know, it's going to take quite a while for you to figure out, right? As it did for the early settlers of the North America to figure out how to get to Santa Fe.

FLATOW: Mm-hmm.

Dr. McKAY: But if they give you a set of instructions, right? They - like Lewis and Clark - they say first go to St. Louis, right?

FLATOW: Mm-hmm.

Dr. McKAY: Then, actually, you're much, much more likely to get to Santa Fe. And so that's one of the reasons I think this cell type is of interest, because it's the cell - if you go from here right out across the continent of the body, you're right - you're next to it. You can go from here, let's say, let's keep this St. Louis metaphor working. You can go to Santa Fe.


Dr. McKAY: You can go to Phoenix. So it's - you're really there. You almost at the Pacific Ocean.

FLATOW: Will this discovery allow us to study diseases in our favorite animal, the laboratory mice?

Dr. McKAY: Yes.

FLATOW: That we had to study, you know, they're bigger more unwieldy animals?

Dr. McKAY: Well, I think what it does is it, yes - it takes this - it makes the mouse model, much more relevant to the human ES cell. Because now, we can test out some of our ideas that will be important for the, sort of, clinical value of early development in a mouse cell which is easier to manipulate and better understood.

FLATOW: Mm-hmm. Because there are some diseases you have to study in sheep, some diseases you have to study in other animals.

Dr. McKAY: Well, there's always going to be a reason, you know. So for example, I mean, if you're interested in cardiac disease…


Dr. McKAY: …you know, a mouse is not perhaps the ultimate model. But there's many basic features of heart development and heart disease that you could study in the mouse. And so, I think the key thing about this cell type is that it is a state, which is stable, and it's a pluripotent cell. So, for example, not only we can use it then as a practical way of going from this cell to more differentiated cells, but we can ask questions that are fundamentally interesting which is, what does it mean to be pluripotent. And a few days ago, many papers - several of them also in Nature - were talking about the idea that you could reprogram an adult cell to make that pluripotent.

FLATOW: Mm-hmm.

So essentially, in the last two weeks, they're have been something of the order of seven or eight reports all dealing with the question of pluripotency. What does it mean to have all this potential to differentiate?

FLATOW: Were these cells taken from a blastocyst that was allowed to develop a little further along? Is that where they were discovered? Does that make them a little more useful in this differentiation stage?

Dr. McKAY: Yup. So one of our colleagues, a guy in Oxford called Richard Gardner who's very famous in this sort of academic world. He had previously done work which showed that you could isolate single cells from a slightly later stage in the blastocyst. So the blastocyst is a stage where the cells are going to give rise to the mouse, which is about a hundred in number. And a day later, the blastocyst has developed further and it has just started to attach to the wall of the uterus. And at this point, there's, perhaps, let's say there's several hundred cells. And two days later, there will be several thousand. So these cells are just about to go through an explosion of growth.

FLATOW: Mm-hmm.

Dr. McKAY: And the stage that we took, and Richard and his colleagues have previously focused on this earlier stage, the stage with a blastocyst is essentially - it's like a kind of spaceship, it's a ball and inside it there's a little cluster of cells attached to the surface, those cells will become the mouse. And then when that attaches to the side of the uterus, at that point, the embryo is going to differentiate and differentiate very fast. And so we went in just to that point and showed that we could grow these cells.

FLATOW: What made you decide that? You're sitting around at the bar having a beer, and say, you know, we should wait another day. I mean, what I'm trying get into is how a scientist thinks about, you know, let's try this or instead of what they try.

Dr. McKAY: Well, it's - I mean, it's a nice story I think. I mean - so one of the key people in this study is a guy called Paul Tesar, who is a student at Case. And now, he's doing a PhD between NIH and Oxford. And so he's the physical link between these labs across the Atlantic. And what we wanted to know is we wanted to know why are the human cells and the mouse cells different? And we thought we should go and look in the mouse to see if we can find a mouse cell that's pluripotent that's like the human cell. And so it took us little time, but that's what we're reporting.

FLATOW: Mm-hmm. But what made you think to wait that extra time, what - you know?

Dr. MCKAY: Because - because previously, to - Richard is very well known. He is one of the people who first manipulated early embryos. And sort of, this is a sort of founding technology for IVF, for example. And they had shown that the standard way of making an ES cell in the mouse seem to be limited, that you couldn't do it after a particular day, 4.5. And we thought, well, if we go in and look just a day later, maybe if we're patient enough and do things somewhat differently, we could in fact, get cells out of that point. And that's why we looked then.

FLATOW: Mm-hmm.

Dr. MCKAY: And in fat, what was interesting was that Paul came back to Bethesda in the summer, and he was learning with us how to grow human cells. And when he went back to Oxford and put these cells into culture, he realized immediately that they were - they looked like human cells and that they weren't growing well under the standard mass conditions. And so he switched them to the human conditions, and then they grew. And so we spent the last three years characterizing them.

FLATOW: Wow. That was a big point in…

Dr. MCKAY: Yeah. It's a - it's interesting. I mean, it's a nice story, actually.

FLATOW: Yeah. Well, we're talking - it is a nice story. We're talking with Dr. Ron McKay this hour at TALK OF THE NATION: SCIENCE FRIDAY from NPR News.

Let's talk a little politics here for a moment. How big an impact does the ban on - the continuing American federal funding ban have on research in your field and this field?

Dr. MCKAY: Well, you know, I mean, this is a - obviously, these issues are sensitive. And they're sensitive in many countries, not just in the United States.

FLATOW: Mm-hmm.

Dr. MCKAY: And the sort of reports that you can reprogram a fibroblast, sort of, in some ways opened up the idea that pluripotency is a state that can be accessed in many different ways. But I mean, in our case at NIH, I mean, we can grow - with federal funds - a restricted number of lines, which actually we find very interesting. And thisis a way that we can contribute to the basic biology of stem cells.

And you know, I mean, as time goes on, presumably, a lot of these issues will become less contentious, I would argue, if - because it's not, I don't think that there's sort of any, sort of overwhelmingly impossible task here. In my view, we will need to understand what pluripotency is. Because it looks like cells can move there relatively easily and it's likely to be an extremely important part of our understanding of cancer.

FLATOW: Mm-hmm.

Dr. MCKAY: So if we have a mouse model, which helps us, that's very, very good. But I spent most of the day today talking about human cells and human stem cells in the brain in particular. You know, it's it's all highly, sort of, technobabble, but it does move us forward. I mean - there's really only basically three reports of pluripotency, right?

There's the original founding report in the mouse in 1980. In the 1990s, there were two or three preliminary reports, and then a report in 1998 of a human ES cell. And then in the last few days, there's our report and there's the report from groups in Boston and Japan that you can generate pluripotency in this completely unexpected way. I mean, that, sort of, gives you a sense of both this sort of novelty and excitement in the field, but also how - I mean, science moves forward by, you know, fairly, sort of, long-term plans.

FLATOW: Yeah. Do you think that you might discover a different kind of stem cell in humans also if you waited a certain amount of time?

Dr. MCKAY: Well, that's one interesting question. We think this is the human cell. That's to say we think it models it. But the human ES cell is not generated from post-implantation embryos, obviously. It's generated from embryos, which were made in the laboratory by IVF. So then an interesting question arises, well, why would the human cell kind of lock in to this state? Why doesn't it look like the earlier mouse cell? I think the answer to that actually is - to do with the way a lot of animals reproduce.

For example, a pregnant elephant can be pregnant for months without anybody being able to find the embryo because they have a way of arresting the very early embryo, it's a phenomenon called diapause. And many, many animals have this. Mice have it. But humans don't. And so what we think at the moment is that the human cell doesn't - can't be arrested early, and so it reaches this slightly later step. And that's the step that we've now isolated in the mouse.


Dr. MCKAY: If that's - obviously, I mean, it seems…


Dr. MCKAY: …a bit difficult to grasp. But…

FLATOW: Well, it's quite interesting. And I want to thank you for taking time to share it with us.

Dr. MCKAY: Yeah. No problem at all.

FLATOW: Good luck to you. Dr. Ron McKay, stem cell scientist at NIH, that's -at that institute he works at the neurological disorders and stroke at NIH in Bethesda.

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