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ELIZABETH FARNSWORTH: A report today in the “New England Journal of Medicine” concludes that a heart broken in a medical sense might indeed mend– that heart muscle cells do regenerate to some extent after a heart attack. Previously it was thought the damage suffered was irreversible. For more on the study we turn to David Finkelstein, Director of Basic Cardiovascular Research at the National Institute on Aging, one of the funders of the study.
Summarize the findings of the study.
DAVID FINKELSTEIN: Well, the study today, basically as you’ve put it, changes paradigms. Before this the model was “heart cells cannot divide.” And the evidence today was pretty clear that heart cells can divide. They basically looked in what is called the confocal microscope to take layers of the heart and look layer by layer, and cell by cell, starting with a marker to be sure that we had a heart cell, a heart muscle cell. Then we had another marker to show that that cell was dividing, to show that the chromosomes were undergoing mitosis — the way everyone knows from their basic Biology text. Then we had another color to show the spindles. Then we had – and we put all of these colors together and we can see, yes, this cell is certainly dividing. What was intriguing is that the division occurred right at the site of a heart attack. This was elevated relative to what you would see in the normal body. So it’s a whole new area for us right now.
ELIZABETH FARNSWORTH: And what changed? This assumption has been around for a long time that these cells didn’t regenerate. What changed that made somebody look at this?
DAVID FINKELSTEIN: Well, you know, if you think the world is flat, you don’t look beyond it. And I think Dr. Ann Bertha has been looking at this for a number of years, and each time the nature of science is each time someone says “how me more, show me more. I’m not convinced.” Scientists are very, very skeptical. And I think today’s evidence is really quite compelling that the cells are dividing.
ELIZABETH FARNSWORTH: This is a very big deal potentially, isn’t it? A lot of people out there have had heart attacks; they have damaged heart muscles. And this means that there is a chance that that muscle could actually be repaired and they could be normal again, is that right?
DAVID FINKELSTEIN: It’s possible that that could happen at some point in the future. I think what we have to be aware of is the heart has many different cell types. In order for the heart to regenerate all the cell types need to be repaired in the same order. The blood vessels to the heart need to be repaired. We need to coordinate everything. When a normal heart attack occurs, we get a scar built up, so even though we see that a heart can do a certain amount of repair, the normal process is not enough. If we can find a way to turn these cells on, that would be very important. And it might be – let me just add one thing – it might be very important when we look at normal aging, where the normal heart decline – can we control how the heart divides?
ELIZABETH FARNSWORTH: How might those cells that are regenerating be turned on?
DAVID FINKELSTEIN: That’s a very, very good question. And we certainly will be – hopefully more people will be looking at that. There could be cytokines or cell factors that are involved; there could be signals about which we know nothing. It really is a whole new area and since people haven’t looked before, since people haven’t asked the question, we don’t know the answers to these things.
ELIZABETH FARNSWORTH: Did the research show the source of the cells that replicate, is that known?
DAVID FINKELSTEIN: No, that’s also a very good point that you asked. We – it could be from the cells within the heart – it could be coming from the circulation. In regular skeletal muscles there are cells called satellite cells, which can repair the skeletal muscle. In the heart no cells of that sort have been identified yet. So certainly where the cells come from is an open question right now.
ELIZABETH FARNSWORTH: I asked that question because I read that there was some prior research by the same people who did this study that showed cells in a mouse from wasn’t it a bone marrow or something?
DAVID FINKELSTEIN: Yes, that’s correct.
ELIZABETH FARNSWORTH: — could be injected into a heart and be made to regenerate that way. That would be very hopeful if it could happen in people, right?
DAVID FINKELSTEIN: Oh, absolutely, but once again, you know, we may be talking – it may be that multiple things are going on. It may be that stem cells from the marrow are normally circulating in your body; that could be one mechanism. It could be that the cells, which are in your heart already are being repaired. It could be cells from different spots in the heart are replicating and mobilizing to remodel the heart; all of these are possibilities. When people have been thinking about possible therapies, the stem cell came to mind. Now we know trying to get the cells to divide. Other people have even thought of putting in skeletal muscle cells, thinking, well, maybe we could get them to become more like heart cells. Once again, it’s really a whole new world for us right now in terms of what the possibilities are.
ELIZABETH FARNSWORTH: You’ve answered this to a certain extent, but I want to ask this right out, because this is the part I don’t understand. If there is the potential for regeneration, why are so many people out there who have had heart attacks who still have injured hearts? And you said it’s partly because everything has to come together, but expand on that, please.
DAVID FINKELSTEIN: Well, in a way it’s more than that. What Dr. Ann Bertha showed was that if – first of all we don’t know for how long the replication continues after the infarct, after the heart attack. So there could be a brief period of time, and then the body stops. There’s other damage going on at the same time. But even at the level of cell division which is occurring, Dr. Ann Bertha calculated that it would take 18 days replace it. That’s a very long time. It may be that we need something to occur under a more rapid time frame. Remember, when you have a heart attack, your heart doesn’t stop beating. You need your heart twenty-four hours a day, seven days a week.
ELIZABETH FARNSWORTH: Is it possible that the cells that regenerate don’t become functioning heart cells that work in the way they’re supposed to?
DAVID FINKELSTEIN: Yes, that’s certainly another possibility. Once again, everything has to be coordinated. What we know now is that cells divide. It’s sort of, if you will, a proof of principle. What we need to do next is to follow up and say, are these cells really functional? Are they coming into the right place? Where are they coming from? How can all of this be coordinated, because, remember, if we get cells growing out of just without stopping, they call that cancer, so that’s not a bargain either.
ELIZABETH FARNSWORTH: So how would you characterize, just briefly, is this really good news, but we still have to be skeptical about what might come of it?
DAVID FINKELSTEIN: Oh, I think it’s very important. Anytime we learn something new, it’s important. You know, 40 years ago a scientist would go in the lab and say I want to cure cancer. But, in order to cure cancer, you have to do something; you have to do an experiment. And here, you know, lots of people say I want to cure heart disease, but you have to start. You have to know what to do. So here at least people can say maybe we can deal with cell division, so I’m sure that there’s going to be a whole generation of people coming along now who are not taught heart cells don’t divide and they’ll be able to ask these questions, and I think that’s going to be a very, very important point.
ELIZABETH FARNSWORTH: David Finkelstein, thanks so much for being with us.
DAVID FINKELSTEIN: My pleasure. Thanks very much.