January 14, 2008
Monday

MINNEAPOLIS -- Researchers at the University of Minnesota have grown a beating heart in a jar.

They used detergents to strip a rat heart of its own cells, leaving behind a white, three-dimensional scaffolding of connective tissue. They then infused it with living cardiac cells from newborn rats, which multiplied and grew into a fully functional heart -- a first in the field of tissue engineering.

"We've figured out how to use nature's own matrix -- chambers, valves, blood vessels," said Dr. Doris Taylor, the lead researcher and director of the university's Center for Cardiovascular Repair. She said that the technique holds promise for growing human tissue to repair not only hearts, but many other parts of the body. It might be possible, she said, to grow whole organs for patients who need a transplant.

Other tissue-engineering scientists around the country said there are enormous obstacles to using the technique for people.

But they described the work as exciting and a landmark.

"It's gutsy. I am very impressed with her going right for the meat of it ... and showing remarkable results," said Dr. Buddy Ratner, a University of Washington bioengineer.

The research was published online Sunday by Nature Medicine, a journal known for publishing cutting-edge science.

Growing human tissue outside the body has been a medical Holy Grail for decades. Progress accelerated in recent years with the use of stem cells, special cells in embryos and adults that can be manipulated to grow into many kinds of tissue. The National Institutes of Health has provided millions of dollars for tissue engineering, but so far researchers have had success with only a few types of human tissue -- primarily bladders, skin and blood vessels.

Though growing heart tissue holds the greatest therapeutic promise of all, it also has proven the most difficult. The heart is a complex structure of chambers, valves and thick-muscled walls fed by an intricate system of blood vessels. And it doesn't just contract; it also twists, as if the muscle were wringing the blood out of the chambers and into the body.

Researchers have tried to grow cardiac patches in the lab to use for repairing damaged hearts. But in order to work, tissue patches must be quite thick, and researchers have not found a way to provide the growing tissue with enough oxygen. And the cells need a three-dimensional scaffold on which to grow, one that allows the cells to contract in the right way to do the mechanical work of a heart.

"Scaffolding is the challenge where we are doing most of our work," said Ratner, who is trying to build an artificial structure with the same kind of material used for contact lenses.

Taylor said that one of the rules in her laboratory is "to give nature the tools and get out of the way." That's how she and her co-researchers came up with the idea of adopting a strategy that's been used elsewhere for smaller parts of the body. They stripped a heart of its cells -- or de-cellularized it -- leaving behind what's called the extracellular matrix.

"When you think about a steak, it's the gristle," she said. It provides both the blood-vessel system to deliver oxygen and the three-dimensional structure. The researchers placed it in a glass chamber and gave it oxygen, nutrients and fluids to pump.

"The cells know they are in a heart and that they should act like a heart," she said.

She has done the same thing with a pig heart and believes it could also be done with kidneys, livers and lungs.

Some experts said that for transplantation, the technique could prove most useful for organs other than the heart.

"Long term, a transplant of the heart is not necessarily going to be the preferred therapy," said Dr. Robert Nerem, director of the bioengineering institute at the Georgia Institute of Technology in Atlanta. "I think there may be more interest in repair of the heart."

The first adaptation for cardiac patients might be for infants born with congenital heart deformities. The technique also could be used to make patches for adults who have lost heart muscle from heart attacks.

But one major barrier to advancing the technique to people is getting body parts to strip. "You have to take a heart to make a heart," Ratner said.

Taylor said it might be possible to use human cadaver organs or pig organs. Pig organs are similar to those from humans and could be adapted, though it might be difficult to get the human body to accept them. That's why Ratner is working with artificial material that would biodegrade in the body, he said.

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