Remodeling Hearts With Stem Cells

Using a type of stem cell taken from bone marrow, doctors are testing whether they can undo heart muscle damage caused by heart attacks. Cardiologist Joshua Hare describes the response of patients who received the treatment, and whether the procedure might be common one day.

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IRA FLATOW, Host:

This is SCIENCE FRIDAY. I'm Ira Flatow. When someone has a heart attack, blood f2low to the heart muscle is interrupted. That lack of blood can do some serious damage to the heart. Over time, a severely damaged heart just can't keep up, and a heart transplant might be a patient's only hope.

But what if that heart muscle could be repaired and blood flow restored, repaired using stem cells? Joining me now to talk more about it is my guest Joshua Hare, cardiologist and professor of medicine at the University of Miami Miller School of Medicine. He's also the director of the Interdisciplinary Stem Cell Institute there. And he's been trying to use stem cells to repair broken hearts.

Welcome to SCIENCE FRIDAY, Dr. Hare.

JOSHUA HARE: Thank you very much, it's a pleasure to be with you.

FLATOW: Thank you. Well, let's briefly go through what happens after a heart attack. There's damage to the heart muscles, and they die.

HARE: That's correct. The - a heart attack is, in essence, a cessation of blood flow to an area of heart muscle. What happens when that blood flow is abruptly stopped for a period of 20 minutes or greater, the heart muscle cells die, and the healing process is one of scar formation.

So similar to the scar you get in your skin when you cut it, a scar like that forms in the heart, and it's intended to repair the damage. But of course scar tissue isn't like muscle, and so the scar can't contract, and permanent damage is caused to the heart muscle.

FLATOW: And then heart failure might kick in.

HARE: Right, so when you have a scar that's big enough, the term that we use in medicine, which is a term most people are familiar with, is remodeling. So the scar tissue causes the heart to blow up by - like a balloon.

Another analogy that people will recognize is that the normal heart is shaped like a football, and the failing heart, after a heart attack has occurred in the heart, becomes shaped like a soccer ball or a basketball. It becomes rounded.

FLATOW: And so it doesn't work as well.

HARE: It doesn't work as well. And that leads to two very, very common medical problems that afflict us in our society: congestive heart failure and a problem called sudden cardiac death, where the heart just abruptly stops beating, for electrical reasons usually.

And so that heart attack leads to a whole host of other very, very serious medical problems.

FLATOW: And once you get this misshapen heart, there's really not much that we can normally do for it, is there?

HARE: Correct. The - so the approach to heart attack currently is to try and restore the blood flow as quickly as possible. And there's an expression: time is a heart muscle. So that's why when you - when folks are having heart attacks, we rush them into the cardiac catheterization laboratory to open that blood vessel as quickly as possible.

The sooner we restore the blood, the less damage there is, but the damage that has already occurred is permanent. And then the other types of treatments we use are lots of medicines to try to make the heart pump easier, and then for those individuals in whom the damage has been so severe, we have to think about heart transplantation or mechanical pumps.

So it's a very, very serious set of consequences that can occur after a heart attack.

FLATOW: But you now report that you've had some success using stem cells to repair the heart.

HARE: Right, so this is - there's a huge amount of enthusiasm in the medical community because of this. And so the idea is, as I said before, that we consider that damage to be permanent. Once the scar has set in, we really can't reverse it. We can only try to ameliorate it.

So the idea with using cells would be okay, we've lost heart muscle and the tiny blood vessels in the heart that feed that heart muscle. Can we coax the heart to regenerate? Can - like the newt that loses its foot, and that foot re-grows, can we get the heart to do that, and can we coax it to do that by using really adult stem cells, stem cells that come from the bone marrow or the heart itself?

FLATOW: And what you did is basically take the patient's own stem cells and just sort of injected it into the right place in the heart and watched the stem cells do their thing.

HARE: Exactly. So you made it sound a little simpler than it actually was...

(SOUNDBITE OF LAUGHTER)

FLATOW: That's my job.

HARE: You summed up 10-years worth of research. But we had to do a great amount of study, studying the biology of the cells. The cells that we used came from the bone marrow, and you're absolutely right. We took the bone marrow from the individuals themselves, and we grow from that bone marrow a stem cell called a mesenchymal stem cell.

It's a constituent of the bone marrow, and we consider it to be an adult stem cell. So we grew those cells, and then we delivered those cells into the region of the heart right between the scar and the normal tissue, so right at the interface, the scar interface.

And we had shown experimentally that that is sort of the sweet spot. If you put the cells in there, they're more likely to have the desired effect. And in a preliminary study, which we published three months ago, we reported a tremendous amount of success. We were very pleased with the results that we got because primarily a key effect that occurred was a reversal of that remodeling, that the way in which the heart had enlarged and blown up like a balloon was dramatically reduced by the injection of the cells.

FLATOW: And have you followed these patients since then?

HARE: Those patients in that study had been followed for a year, and we do continue to follow them. But more importantly, we're doing a follow-up study of 60 patients, and in that much larger study, we will have a - once the results are in from that study in about a year's time, we'll have a much greater certainty about the outcome because in the follow-up study, we'll also be measuring the patient's quality of life, their need for hospitalization.

We'll be getting a very detailed safety profile on how they've done with the cells, and we'll just in general be getting a lot more information.

FLATOW: Now, you said in your work that you saw the change very quickly, within a matter of weeks.

HARE: Well, actually the first time point that we measured was three months. So at three months after the injection, we could already see that the damaged area had started to contract again. And this was probably one of the most exciting parts of the finding because as I said before, it's a scar, and we know that scars don't beat and therefore don't contract.

We confirmed very carefully in the study that it was a scar. We used the best possible imaging technology, with MRI imaging, to really prove that it was a scar. And then at three months, we could detect evidence that that scar tissue had started to contract. And then that was followed three months later, at six months, by the reversal of the remodeling, that the heart size started to become smaller again.

FLATOW: Let me jump ahead in time a little bit and say that your technique proves to be successful and useful, how easy would it be for you to teach other cardiologists to do the same thing to other patients? You get the point I'm driving at?

HARE: Absolutely. This is easy. This is, you know, this is the future of medicine. To be specific, this is something that can become widely available at hospitals throughout the United States.

The limitation will be training. Just like new techniques came along like angioplasty, the future and eventual cardiologists will have to be trained to do the injections. But it's done with a catheter, just the way an angioplasty is done. So doctors can be taught.

And then of course we have to find the optimal cell. What we have right now is what we would consider a first-generation cell. It seems to work quite nicely, and it can be also generally produced. And what we expect coming down the pike will be improvements on the way in which the cells are prepared.

FLATOW: Do you think other organs in the body could be regenerated the same way?

HARE: We do. This - the idea that the adult organs have stem cell compartments is becoming more and more generalized. A group of doctors at the Brigham and Women's Hospital in Boston, led by Dr. Piero Anversa, recently showed that the lung also has stem cells. And so we're hopeful that we can repair lungs, brains, kidneys and on and on through the same general principle of delivering adult stems cells to those organs.

FLATOW: And so you basically are trying this out just relatively few patients, just something like 100 patients so far. And you're looking to see what the results are and maybe expand it out if it works.

HARE: Exactly.

FLATOW: Wow. Are you using anything proprietary here? I mean, where's your research funding come from?

HARE: So thank you for asking that question. It's such an important question. We're thrilled to be able to say that the lion's share of our funding has come from the National Institutes of Health. And it's so important to recognize that this is such a new area, that it's so important for the NIH to fund research in this area, and they have. And we're hopeful that the NIH will continue to fund.

Of course as the way things go, there is technology transfer, and one example of the technology of a technologic advancement we're using is the catheter. The catheter we've been using is manufactured by a company called BioCardia. And they've very graciously donated their catheters to our research, along with a small amount of the funding. The lion's share comes from the NIH, but the catheter company, of course it wants to see their technology advance has also supported it.

FLATOW: One last question: How are the patients doing that have been through this? Are they noticeably different?

HARE: Well, this is always the trick, and this is why it's so important to do this in a scientifically rigorous fashion, with placebos and with what we call blinding. So we - in our upcoming 60-patient study, we have a placebo group, and the patients are blinded to whether or not they're getting their cells.

It's very important to do that to prove the clinical effects, and one of the clinic effects would be the patients reporting that they feel better.

A lot of our patients have said that they feel better. So patients are reporting noticeable improvements, but we need to be absolutely sure that those improvements are coming from the cells, and we can report that information back to the Food and Drug Administration and working in conjunction with them advance the technology as quickly as possible.

FLATOW: Well, good luck to you, Dr. Hare.

HARE: Thank you so much for having me on the show.

FLATOW: You're very welcome. Have a good weekend. Joshua Hare, cardiologist and professor of medicine at the University of Miami Miller School of Medicine and director of the Interdisciplinary Stem Cell Institute there.

We're going to take a break, and when we come back, we'll be talking about wildlife of our bodies, yeah. Stay with us. I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.

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