Growing a heart valve
Pitt bioengineering professor Michael Sacks is working to grow heart valves in the laboratory, working with animal models.
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Sheep aren't just famous in the biomedical world because they have been cloned.
It turns out they are also vital for heart valve research, says Michael Sacks, a biomedical engineering expert at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.
Sheep grow quickly and tend to suffer from the same calcium buildup on their heart valves that humans do, Dr. Sacks said. That makes them ideal for testing whether new heart valves can be grown in the laboratory using tissue engineering techniques.
Working with researchers at Children's Hospital of Boston, Dr. Sacks is using the sheep's own blood cells to grow heart valves in the lab around polymer scaffolding and then implant them, where they have worked successfully for up to 20 weeks.
The ultimate goal is to create heart valves for children using their own tissue, a technique that is designed to allow the valves to grow along with the children's bodies, said Dr. Sacks, the William Kepler Whiteford professor at the McGowan Institute.
That would overcome a major problem children with heart valve problems now face.
Many of them get valves from human donors, but those transplanted valves don't grow with the children, who then have to undergo anywhere from two to five valve replacement surgeries before they are adults.
The other advantage of lab-grown valves would be to cut down on the calcium buildup that causes current prosthetic tissue valves to wear out.
Calcium accumulation is a bigger problem in children than adults, because their bodies are still actively metabolizing it for their growing bones.
In addition, the implanted tissue valves children now get, whether from humans or animals, are cleansed in a substance called glutaraldehyde to prevent them from causing an immune reaction. But glutaraldehyde also becomes a magnet for calcium molecules, researchers say.
Right now, Dr. Sacks and his team are using sheep's blood to grow a cellular matrix along polymer scaffolding. After the engineered valve is put into the sheep, their own tissues start to replace the polymer.
Tests so far have shown that this polymer replacement process is occurring in sheep after five months, when they are almost adults, he said, but has not yet proven whether the valves are growing at the same pace as the sheep's hearts.
Other research groups in America and Europe are tackling this problem with another approach.
They are trying to rid human donor valves of all the endothelial cells that cause an immune reaction in the patient, in hopes that once the valve is put in place, the child's own cells will start to infiltrate it.
Whichever approach works best, it may take another 10 to 30 years before these valves are widely available because of the need for further research and then clearing steep regulatory hurdles, Dr. Sacks said.
In the meantime, there are at least two other innovations under way in heart valve surgery, said Dr. Wolf Sapirstein, chief medical officer for the division of cardiovascular devices of the federal Food and Drug Administration.
Dr. Sapirstein said trials are under way to install prosthetic heart valves by snaking them through blood vessels with catheters while the heart is still beating. That sidesteps the problem of having to stop the heart and put the patient on a heart-lung bypass machine while the valve is implanted.
The other initiative is experimental work to develop extremely thin, pliable metal valve leaflets that could last much longer than tissue valves but not cause the kind of clotting that current metal valves do.
In any event, Dr. Sacks advises people to be patient.
The problem in this field, he said, is that "everybody wants the instant gun and they need to understand that valve development is going to be very slow because most of the low-hanging fruit has already been achieved.
"To make a substantial improvement now is a very tall order and will take a very long time."
First Published March 12, 2008 12:00 am