Heart Beats- Heart Patches

Heart Beats- Heart Patches

It's a Band-Aid for the heart.

Heart disease is the leading cause of death for both men and women. Five million Americans are living with heart failure and 715,000 will have a heart attack this year. Now, scientists are working on a new way to repair damaged hearts.
It weighs ten ounces, on average beats 72 times a minute, and pumps 2,000 gallons of blood through the body every day. The heart is an amazing organ, but when it encounters an attack, this body part falls flat.
“The heart is very poor at self-repair.  It’s one of the least regenerative organs in the body,” Charles Murry, MD, PhD, Professor of Pathology, Bioengineering, and Medicine/Cardiology, Murry Lab, UW Medicine, told Ivanhoe.
Researchers at the University of Washington are studying a new way to fix hearts.
“Our idea is to use stem cells in such a way that they can actually re-muscularize the heart after it’s become injured in some way,” Dr. Murry said.
First, they place embryonic stem cells along with other special cells in a petri dish so they grow and divide.
“In about two weeks, you will see in the dish spontaneous beating human heart muscle,” James Fugate, Lab Manager/Research Scientist, Murry Lab, UW Medicine, told Ivanhoe.
Beating human heart muscle cells are put into a matrix, where they form into a heart patch.
“We can take these patches and attach them to the surface of the heart, kind of like a muscular Band-Aid,” Dr. Murry said.
The patch helps cells form new tissue in the heart. It could be used in patients who’ve had a heart attack or those with heart failure.
“It’s like growing back parts of your heart that you lost due to disease,” Dr. Murry said.
The heart patch is being studied in the lab in animals, where it prevented heart failure after a heart attack, beating 120 times a minute in monkeys. Dr. Murry hopes to see the same kinds of results in humans, and if they do, it will revolutionize the way our most vital organ heals.
One of the major obstacles researchers need to overcome is the likelihood that people’s immune systems would reject the embryonic stem cell transplant unless they take medications for the rest of their lives. Dr. Murry hopes to one day create new tissues from a person’s own cells.

BACKGROUND: Heart disease is the number one killer of both men and women in the United States and has become one of the most serious public health issues facing Americans. It is a broad term which refers to a variety of related heart conditions, including heart attack, ischemic stroke, and heart failure. The disease kills 600,000 people each year, which is about one out of every four deaths. The most common type of heart disease is called coronary artery disease. It occurs when cholesterol deposits, called plaque, build up in your arteries, causing them to narrow or become blocked. The narrowing or blockage can lead to heart attack, heart failure, or arrhythmia. Once any of these occur, the heart has a difficult time rebuilding its strength. (Source: http://www.cdc.gov/heartdisease/coronary_ad.htm)
CAUSES: Heart disease is the result of a variety of factors, some of which are out of your control. These include age (82 percent of those who died from coronary artery disease were over the age of 65), gender (males are at a higher risk for having heart attacks, and at earlier ages than women), and genetics (those with a family history of heart problems are much more likely to develop other risk factors). But there are some factors you can control. These include weight, tobacco use, high blood pressure, high cholesterol, and diabetes. (Source: http://www.heart.org/HEARTORG/Conditions/More/MyHeartandStrokeNews/Coronary-Artery-Disease---Coronary-Heart-Disease_UCM_436416_Article.jsp)
NEW TECHNOLOGY: Researchers at the Murry Lab at the University of Washington in Seattle, are now researching the ability of embryonic stem cells to treat the effects of heart disease. Embryonic stem cells have the ability to turn into any kind of cell in the body. So researchers have been able to use these cells to create beating heart cells outside of the body. These cells could one day be injected into the heart, and could essentially act as a Band-Aid, covering the parts of the heart injured by a heart attack. The cells would be able to re-muscularize the heart, which it cannot do by itself. These cells would be used in an effort to prevent heart failure in patients who have had a heart attack. Currently, the stem cell treatment has only been performed on mice, guinea pigs, rats, and non-human primates. Doctors believe it will be 4 years until human trials. (Source: Dr. Charles Murry)
FOR MORE INFORMATION, PLEASE CONTACT:

Charles E. Murry, MD, PhD
Arra and Eva Woods Professor of Pathology, Bioengineering and Medicine/Cardiology
Director, Center for Cardiovascular Biology
Co-Director, Institute for Stem Cell and Regenerative Medicine
University of Washington
(206) 616-8685
murry@uw.edu


Chuck Murry, MD, PhD, Professor of Pathology, Bioengineering and Medicine/Cardiology, Murry Lab, UW Medicine, talks about a new procedure that is healing hearts with patches.
What got you interested in heart patches?
Dr. Murry: I’ve been working on stem cell approaches to repair the heart for the better part of 15 years now.  I sort of grew up with this field, it was a radical notion when we first proposed it in the 1990’s and now it’s positively mainstream.  
So, what are you developing with heart patches?  
Dr. Murray: So, our goal is to somehow harness stem cells in such a way that they can make the heart heal better after a patient has a heart attack or a myocardial infarction.  Usually, the heart is very poor at self-repair.  It’s one of the least regenerative organs in the body and so it heals by scar formation rather than growing back new muscle.  So, our idea is to try to use stem cells in such a way that we can actually re-muscularize the heart after it’s become injured in some way. In doing so, we hope to keep patients from developing heart failure after they have a heart attack for example.  We have been working with a variety of different types of stems cells. The ones that work best in our hands are the most primitive ones, either the embryonic stem cells or the reprogrammed type. By taking lessons from embryological development, we’ve learned how to turn these cells into essentially infinite numbers of beating human heart muscle. So, we can grow petri dishes full of beating heart muscle and then we’ve learned how to transplant those into the hearts of injured animals where we can get them to form grafts of human heart muscle in these animal hearts.  One of the things that we’ve learned is that this can keep the animals from developing heart failure after a heart attack. It’s  like growing back parts of your heart that you lost due to disease. 
How does this differ from using the stem cells to make new arteries that go into your heart? 
Dr. Murray: So, people are trying to do different aspects of treating cardiovascular disease.  The number one cause of heart attacks is disease of the blood vessel and one of the things that the surgeons always lament is that we don’t have good enough vessels to use as coronary bypass grafts. So, one of the things that people in tissue engineering want to do is to be able to grow new blood vessels that would be the right size to use as a graft for a patient with coronary artery disease, for example.  So, we’re one step downstream of that.  We’re not trying to grow the new big pipes to the muscle; we’re trying to grow the muscle itself; the stuff that’s been lost downstream when a patient has vascular disease. 
Is it really like making a patch for damaged parts of your heart? 
Dr. Murray: So, we’re doing this in a couple of different ways.  The area that we are furthest along is using a suspension of cells that we literally just inject into the damaged wall of the heart with a needle and syringe. Remarkably, the cells are smarter than the people who are working with them, and they know how to make tissue.  So, they start out as a suspension, but then they start to self-organize and the muscle cells will connect with other muscle cells and start to form muscle tissue within the damaged region of the heart.  We’ve also shown that if we include blood vessel cells, and there are these blood vessel cells will form a vascular network.  They self-assemble into capillaries so the vessel cells talk to the vessel cells and the muscle cells talk to the muscle cells and nature sorts a lot of this out for us.  So, we get a break from Mother Nature in that regard.  So, that’s the first approach; just taking a suspension of cells and delivering it to the wall of the heart.
A more complicated, but potentially more powerful approach that we are working on is the heart patch approach where we are building a chunk of three dimensional human heart muscles in a dish. We can make this variety of shapes and sizes.  The limitation really gets to be how you get nutrients to the stuff.  Unless you have flow going through it, it can only grow so big and then it otherwise just diffusion from the outside is limiting for it.  However, we can grow decent size chunks of human heart muscle. I could grow something as big as my thumb nail, for example, in a patch and then we can take these patches and attach them to the surface of the heart, kind of like a muscular Band-Aid.  We are working on strategies to get this to connect up and get integrated so that it will beat in synchrony with the surrounding heart muscle. 
What kind of patient would benefit the most from this?  
Dr. Murray: There are a number of patients who might be able to benefit from re-muscularization kind of stem cell therapy.  The first patient that we’d think about is somebody who has had a recent heart attack or recent myocardial infarction.  And I think what we might be able to do for them is the easiest because those are the patients who have not yet developed heart failure. So prevention is always easier than cure. If we can prevent somebody from going into heart failure after they have had a heart attack, that would be our first and foremost goal.
Now, with that, would you inject it into the heart?
Dr. Murray: That is where we are going to start.  We are going to start by injecting cells directly into the wall of the heart in patients who have had relatively recent myocardial infarctions. 
How fast do these things grow?  
Dr. Murray: They grow really fast in the dish, when they are in the unspecialized or undifferentiated state.  They grow like crazy.  They’re immortal and we can grow them up by the vat full.  When they turn into heart muscle, their division slows way down and after we transplant them in, we get a few more rounds of cell division, which helps a lot to repopulate the damaged region and then they slow down.  One of the concerns initially was what if we grew a tumor in the heart of a patient.  We would never want to take some poor patient who had had a myocardial infarction and then give them an uncontrolled tumor growth, but the work that we’ve done to date suggests that’s really not a problem.  We’ve been able to control the cells well enough that if we could get them committed to being muscle as opposed to being unspecialized, they behave pretty well once we transplant them in. 
So, this has not been in patients?
Dr. Murray: This has not been in patients. 
How would you transplant them in?
Dr. Murray: Let me back up because the work that we are doing with embryonic stem cells and pluripotent stem cells have not been in patients yet, but people have been putting different cell populations into human hearts for the better part of a decade now. 
I haven’t heard of pluripotent stem cells.  What are they?
Dr. Murray: Pluripotent means you can turn into basically any cell type within the body. 
Where do you get them?  
Dr. Murray: There are two basic flavors of pluripotent stem cells; one is the embryonic stem cell and that’s the one that’s famous and somewhat controversial because embryos have to be destroyed in order to generate the cells.  More recently, scientists have learned how to take adult cells from skin; we can take cells from blood; and we can take cells that you slough off into your urine from the lining of your bladder and we can reprogram them back to sort of a ground state, to a very primitive stem cell state and then these cells once reprogramed can go into virtually any cell type in the body.  So, we’ve set the clock back to zero basically and we can take any new set of directions we want going forward. So, I think 5, 10 years down the road, this is going to be an extremely useful technology for regenerative medicine. 
So, you just have a heart attack and you inject this into the heart. In your theory, how long until it actually helps the heart?  
Dr. Murray: So, what we have found is, at least in our animal models, so far, the benefits are very soon.  What happens when a patient has a heart attack is their cardiac function starts to go down fairly rapidly.  And what we’ve found is that when we transplant these stem cell graphs into the heart, within days these two curves start to diverge.  The control heart function goes worse and worse; the ones we’ve just put a placebo or a vehicle into.  The ones that we’ve put our human cardiac muscle cell grafts into, they arrest the decline and sometimes they start to go back up to actually regain the function that they’ve lost. 
Does it continue to go up?  
Dr. Murray: It continues to go up for a while and then it plateaus and we’ve not yet gotten it back all the way, so this is all still a work in progress.  We’ve not gotten it back to where they were before they had the heart attack. 
If everything keeps going on the path, when do you think like human trials?
Dr. Murray: We are looking to do a first in human clinical trial in probably 4 years. 
Would you take the stem cells directly from the patient?
Dr. Murray: Down the road, we would love to be able to take stem cells from the patient, grow them up, and put them back into the patient.  The biggest advantage to doing something like that would be that they would be recognized as self by the immune system.  If we take cells from someone else, or from an embryonic stem cell source, the immune system is going to see this. That means it will probably be from another person or so called allogeneic cells, probably the immune system will recognize them and we’ll have to give the patients drugs to suppress their immune system initially to make them tolerate the cells.  So, it will be like regular transplant medicine where you do hearts and kidneys and things like that where patients have to have some type of immunosuppression. 
Alright, what’s next for this?  
Dr. Murray: Well, the next thing is to get this working in larger animals that we think will be predictive of the human response.  We’ve made this work in mice.  We’ve made it work in rats.  We’ve made it work in guinea pigs.  Now, we are starting to work in nonhuman primates and it looks promising, but it’s still the early days. 



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