University of Minnesota researchers grew a rat heart in a
landmark effort that may foreshadow the ability to grow tissue to repair
organs, or even create organs for transplant.
By JOSEPHINE
MARCOTTY, Star Tribune
Last update: January 13, 2008 - 11:07 PM
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.
A challenging task
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.
Many healing possibilities
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 Georgia Institute of Technology in Atlanta, Ga. "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.
Those heart problems are usually identified before the child is born. Stem
cells from the umbilical cord and the amniotic fluid could grow the heart
parts the baby needs.
"The biggest hurdle is cell type," said Dr. William Wagner, professor of
bioengineering at the University of Pittsburgh. Since Taylor is an expert in
stem cell biology, "I bet she is well equipped to try that," he said.
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.
But most importantly, said Dr. Tim Henry, a cardiologist and researcher
with the Minneapolis Heart Institute, Taylor has brought a startlingly new
approach to an area of medicine with vast but largely unproven potential.
"The problem with science is that you need to take big steps," he said.
"Some things we think are not possible, and someone has to think outside the
box and prove that they are."
Josephine Marcotty 612 673
7394
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