Researchers Grow Rat Heart in Laboratory

Researchers report that they've been able to build an artificial beating rat heart. The new heart is weaker than an ordinary heart, but the researchers hope that the technique could one day be used to help grow replacement organs for patients needing heart transplants.

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IRA FLATOW, host:

This is TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.

A bit later in the hour, writer Diane Ackerman joins us with the story of "The Zookeeper's Wife."

But up first, an amazing tissue engineering story that grabbed headlines this week. A team of scientists brought a dead rat heart back to life. The researchers took a rat heart, stripped it of its cells, and reseeded the remaining valves and structural parts with heart cells from a newborn rat. And within days, the heart was beating. And within two weeks, it was pumping small amounts of blood. Research is out in this week's issue of journal Nature Medicine.

And the study's lead author is here to talk with us about it. And if you'd like to join us, our number is 1-800-989-8255. Also, in Second Life, you can go to our New Island Science Friday there. We're at sciencefriday.com. Find a little click on the SLurl there to go to Second Life.

Doris Taylor is the Bakken professor and director of the Center for Cardiovascular Repair, University of Minnesota, in Minneapolis. And she joins us today. Welcome to SCIENCE FRIDAY, Dr. Taylor.

Doctor DORIS TAYLOR (Director, Center for Cardiovascular Repair, University of Minnesota): Thank you. It's a pleasure.

FLATOW: This sounds like something straight out of a science fiction movie.

Dr. TAYLOR: In some ways, it does. We had a great time, but we really wanted to make a difference in the lives with people with chronic disease.

FLATOW: Uh-huh. I think, when you say you stripped out - it was a dead rat heart that had no cells in it. I think a lot of us think that whole heart has living cells in it.

Dr. TAYLOR: Right and we were surprised ourselves. So, basically, we took a heart, we used soap, same thing as shampoo, washed it through the heart, and washed out cells and lo and behold, there was something left that looked like a ghost heart.

FLATOW: Wow.

Dr. TAYLOR: It was remarkable. Still looked like a heart, had all the chambers of the heart, but obviously, it wasn't alive anymore.

FLATOW: Now, tell us - take us through the rest of the story.

Dr. TAYLOR: So, next, we took cells from a newborn rat, just like you said, transplanted those into the wall of the new heart, and then grew that in the laboratory for about a week. We hooked it up to a pacemaker because we wanted to make sure it had the best chance to beat and over time, it started getting stronger and stronger. And by a week or so out, it was pumping. It was amazing.

FLATOW: Wow. I mean, just having a mental image - and we actually have a video of it on from your laboratory on our Web site. It's sciencefriday.com if people want to watch it. How - when you say it was pumping, did it become functional?

Dr. TAYLOR: It did. So, the really encouraging thing for us is that we think we've made a step forward in maybe creating a heart that can be used for transplant one day.

FLATOW: How do you keep it alive outside of somebody?

Dr. TAYLOR: You know, heart cells know how to live in a dish, but we have to get them food and nutrients. And so, we used the blood supply, the same blood vessels we had used to put the soap into the heart and washed the cells out, we used to feed the new cells once we transplanted them in.

FLATOW: So, you, like, cooked up a little miniature heart-lung machine through it?

(Soundbite of laughter)

Dr. TAYLOR: You know, in a way, we did. That's exactly right. We made all the vitamins and minerals that those heart cells needed, put them in solution, and let the heart pump it. And it pumped it around to itself and it really was like creating an artificial circulation in the lab.

FLATOW: Would it have been strong enough to put it back into the rat and let it work?

Dr. TAYLOR: You know, this one wasn't, but we only let it go for a couple of weeks and we didn't try to make it strong enough. So, our hope now, our belief now, is that it's really a matter of adding more cells and letting it go longer. And we're on the way.

FLATOW: Are you working with rat hearts or other hearts now?

Dr. TAYLOR: You know, we're working with both. We're working with rat hearts, but because we want to be respectful of resources. But at the same time, if we're going to make this happen, and if we're going to make it happen for patients with disease, we need a human-size heart. So, we've moved to pig heart and the hope is, that if one day, someone like you needs a heart, we can take a pig heart or a heart from a human that couldn't otherwise be used as a transplant heart, and strip it of cells, and then take your cells. Your stem cells from bone marrow or blood, or maybe even a little piece of - a little biopsy of heart. Grow them in the lab, transplant them and create a heart that matches you.

FLATOW: Hmm. Why not reseed the person's own heart?

Dr. TAYLOR: You know, that's the next alternative, but the truth of the matter is, if we were going to do that, we'd have to have a way to keep somebody alive the period of time it takes to do that. Obviously, with artificial hearts and mechanical devices, that may very well be an option in the future.

FLATOW: Mm-hmm. So, what you're talking about then is creating spare parts then?

Dr. TAYLOR: That's right. creating a heart for someone who needs it, who has heart failure.

FLATOW: Mm-hmm. Could we take a, let's say, a cadaver heart or someone who's heart is not quite good enough for a heart transplant and tweak that up a bit?

Dr. TAYLOR: That's our goal. We're moving in that direction. There's no reason - you know, in some ways, it's a whole lot easier to do it with a human-size heart than it is to do it with a rat heart. It's larger, it's easier to handle and actually it's technically less difficult. So, yes.

FLATOW: Wow. Let me go to the phones. We got a call in here from Anne(ph) in Berkeley. Hi, Anne.

ANNE (Caller): Hi. I hope this isn't a very obscure question. It's really simple, actually. There's stem cells and then there are the cells that are located like in your cheek or in your, on your nose, or some other part of your body. I think they're called somatic cells - I don't know what they're called. But I get the impression that there are gradations of specialism, like, you know, you have a stem cell and then you have a heart-destined stem cell.

FLATOW: Mm-hmm.

ANNE:: And then you'll have a valve, heart valves that I…

FLATOW: Right.

ANNE: …don't know, or…

FLATOW: Wait, do you - Anne, do you have a question here, Anne? Anne, do you have a question?

ANNE: Are there degrees of steminess(ph)?

FLATOW: Ah, good question.

Dr. TAYLOR: Sounds like you know as much about stem cells as we do.

(Soundbite of laughter)

Dr. TAYLOR: Truth of the matter is, yes, there are stem cells and all a stem cell is is a cell that can make more of itself and make other kinds of cells. And then there are cells we call progenitor cells, that have already started to make some kind of cell. One of the really nice things about what we're doing is because we can do this with any organ, with kidney, liver, lung, heart, almost - well, virtually any organ that gets a blood supply, we can now put the same stem cell in every organ and say, is it nature or is it nurture? Does the organ tell it what to do or does the stem cell know already?

FLATOW: Mm-hmm. Will my body reject this organ, if you make it?

Dr. TAYLOR: You know, if we - the hope is that if we take your stem cells and we put them on this matrix, that it'll make the matrix invisible to your body.

FLATOW: Hmm.

Dr. TAYLOR: The truth of the matter is, we don't completely know yet, but what we do know is that decellularized pig valves are used right now for transplant into humans. So, it's not unreasonable to think that by getting rid of the cells and putting your cells in, we could make something that matched your body.

FLATOW: Mm-hmm.

Dr. TAYLOR: And even if you needed drugs to prevent rejection for a short period of time, the hope is that over time, as those proteins, and scaffold, we call it get replaced, they'll become your proteins, and ultimately, it'll be your heart.

FLATOW: You know, it's - we ask so many times in invention and this is another instance.

(Soundbite of laughter)

FLATOW: You know, it's - we have had so many times in invention and this is another instance?

Dr. TAYLOR: You know, in some ways, it's pretty straightforward and in other ways, it's pretty outside the box. And I'm just lucky to be part of a team that's willing to work outside the box.

FLATOW: What do you mean it's outside the box?

Dr. TAYLOR: You know, nature has done a great job making these organs and it became really clear to us. We couldn't build one, we weren't smart enough or didn't understand it well enough. So, we just took the simple approach, let's let nature do it for us. And I think in some ways, that's really an outside-the-box phenomenon because it's a whole lot more fun to think you can build it in a lab.

FLATOW: Could you not make an artificial version of that structure, you know, that's left over and then use that as a grid work to grow cells on?

Dr. TAYLOR: You know, in theory, we could but my guess is that would take me the next 20 years of my career. And right now, we have something that's already perfect, nature's done it for us and in my mind, it's time to move forward and see if we can make a difference in the lives of people with disease.

FLATOW: And what do you need now to continue?

Dr. TAYLOR: Obviously, resources.

FLATOW: Money.

Dr. TAYLOR: You know, federal funding for science is at the lowest it's been in my lifetime. And doing an experiment on a rat and doing an experiment on the human-sized heart costs about 20 times more. So, we need to move forward. We need people, we need ideas and we need money.

FLATOW: But…

Dr. TAYLOR: But what, you know what? We're committed to doing it and we're going to do what it takes to get what we need and move forward.

FLATOW: So you have a plan?

Dr. TAYLOR: We are making a plan. Yes, we have a plan.

FLATOW: And where do you go next on your plan?

Dr. TAYLOR: Well, I think next is really trying, take hearts with human cells. There's no reason we can't except resources, so we're - that's underway at the University of Minnesota. We're, you know, we're lucky, we're committed and we're going to move it forward.

FLATOW: So, you got pig hearts sitting in little dishes there hopefully…

Dr. TAYLOR: Well, not little dishes…

FLATOW: Big dishes.

Dr. TAYLOR: …they're pretty large. And yes, we've got pig hearts that we've drained of cells and the next step is trying to put human cells or even pig cells back and see if we can make them invisible to…

FLATOW: How long does it take to reconstruct the heart?

Dr. TAYLOR: In a rat?

FLATOW: Yeah.

Dr. TAYLOR: A couple of weeks, a few weeks. In a pig, it's going to take longer.

FLATOW: Just a couple of weeks.

Dr. TAYLOR: Well, so far, we've gone out about 40 days on these, and so have we hit the homerun yet? No. But we've certainly made major progress. And I have to say it's been a team effort. There are people who slept in the lab, lived -lab, lived in the lab and there's a whole group of people, including Dr. Ott, who lived, eaten, and breathed this.

FLATOW: Wow. So, it does take a village to make a heart.

Dr. TAYLOR: It does take a village to make a heart and the kidney and a liver.

FLATOW: Well, looks like you have an interesting first start there and I imagine there are other people working on the other organs, also.

Dr. TAYLOR: You know, I'm sure there will be, going forward, because clearly, heart disease is not the only problem in this country or the world.

FLATOW: Well, we will be waiting to hear your results and if they go as well as you say, it shouldn't be very long to hear about them.

Dr. TAYLOR: You know, I don't want everyone to think that we know all the answers - we don't. But what we're very optimistic, we moved from idea to the first heart beginning to beat in the lab in a year and that's pretty remarkable. So we think we have the right ideas and we are beginning to understand the science and hope to move forward in a safe but effective way.

FLATOW: Dr. Taylor, good luck to you and thank you for taking time to be with us today.

Dr. TAYLOR: Thank you so much.

FLATOW: You're welcome.

Doris Taylor is professor and director of the Center for Cardiovascular Repair at the University of Minnesota in Minneapolis.

We're going to take a short break and when we come back, we're going to talk about "The Zookeeper's Wife." A really interesting story about what happened to the zoo in Poland in Warsaw after the Nazi blitzkrieg and the animals, and it's a great story, so stay with us. We'll be right back after this short break.

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FLATOW: I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.

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Researchers Grow a Beating Heart

Two images of a rat heart during experiment i i

The process of building a new heart starts with a cadaveric rat heart, shown above. As cells are washed away, a whitish skeleton of soft tissue is left behind. Thomas Matthiesen hide caption

itoggle caption Thomas Matthiesen
Two images of a rat heart during experiment

The process of constructing a new rat heart started by soaking the heart in a detergent solution to remove old cells (top row). Once the cells were gone, the heart became translucent (top right). When living cells were added, they grew on the structure left behind (bottom).

Thomas Matthiesen

A custom-built replacement organ sounds like science fiction, but researchers working in Minnesota have figured out a way to construct a beating rat heart in the lab.

Building a whole heart is much more challenging than simply growing heart cells in a dish, something that labs can do routinely. The heart is a round, meaty muscle the size of a fist, with four chambers and a complicated network of blood vessels.

"The heart is a beautiful, complex organ," says Doris Taylor, director of the Center for Cardiovascular Repair at the University of Minnesota in Minneapolis. "We realized pretty quickly that we weren't going to be able to figure out how to build that in a dish."

Taylor and her colleagues knew that when nature builds a heart, the cells attach to a kind of scaffold, or frame, made of things like proteins. "It's basically what's underneath all of the cells, the tough part that the cells make to hold each other together," she says.

The researchers decided to see if they could take a dead heart and remove all of its cells, leaving this scaffold behind. The scientists thought they could then use the scaffold to construct a new heart out of healthy cells.

Harald Ott, who now works at Massachusetts General Hospital, was working in Taylor's lab, and he took this on as a kind of side project. He started treating rat hearts with all kinds of different solutions.

"We had a big chemical shelf in the lab, from A to Z," recalls Ott. "So I started using all sorts of chemicals starting at A."

He tried enzymes, but they dissolved the heart. Other chemicals made the heart swell and change shape. Then one day, Ott grabbed a chemical known as SDS. "It's a regular component of shampoo," he says. "It's a soap."

At first nothing seemed to happen. Then, patches on the heart began to turn white. The red part, the meaty part, was disappearing.

"You can see the detergent working and making the heart literally translucent so it turns into a jellyfish sort of appearance," says Ott, who explains that it looks just like a jellyfish shaped like a heart, with all the organ's intricate 3-D structures.

Then Ott and his colleagues took heart cells from newborn rats and put them onto the scaffold. The cells stuck and started to grow. The heart became red again.

But it didn't beat, so the researchers attached a tiny pacemaker and the heart began to rhythmically wiggle. After a while, it would beat even without the pacemaker. Taylor says it was an amazing thing to see.

"It was the best we could possibly hope for," she says.

Still, the heartbeat wasn't that strong, just 2 percent of the pumping action of an adult heart. Taylor thinks they can improve on this work, reported in the journal Nature Medicine.

And she's started working with pig hearts, which are about the size of human hearts.

"One possibility is that we could take a pig heart scaffold and then use your cells to repopulate that," Taylor says. She notes that since cells are always slowing replacing their scaffold, eventually the heart would be entirely human.

Taylor's lab is also exploring this approach for other organs. Her group has shown that it can get a similar kind of scaffold from the liver, lungs and kidneys.

"This approach does address some of the major challenges that one faces in thinking about how to generate a functional heart that really has the structure and function of the native heart," says William Wagner, a scientist at the University of Pittsburgh who studies technologies that can replace or restore heart function.

But Wagner cautions that this is just a first step and there's lots of work to do before people could get organs grown in a lab. "The limit right now is the cells," Wagner says, noting that this experiment used cells from newborn rats.

For this approach to be useful in people, scientists will have to find a human cell — preferably one that can be taken from an adult patient — that is very good at growing into new heart tissue.

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