Breakthrough in Tissue Engineering: 'Ghost' Heart Reborn with Stem Cells

[Guest guest]

[This is a big deal. It has no practical value now, but the seeds (so

to speak) are sown for future research. It's a proof-of-concept

experiment that worked better than many had hoped.]

Published online 13 January 2008 | Nature | doi:10.1038/news.2008.435

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Ghost heart has a tiny beat

Rat organs can be stripped of their cells and regrown to pump blood.

Heidi Ledford

A rat heart turns ghostly pale when stripped of cells hearts, stripped

of their cells by detergents, have been used as a scaffold to engineer

a bioartificial heart, which can amazingly pump a little like the

original organ.

With further development, the method may one day be used to repair

heart damage or even generate new hearts for transplantation.

Cell-free hearts from pigs, for example, could serve as scaffolding to

grow a heart with human cells, researchers say, because pig hearts are

of a similar size and complexity to human hearts.

The heart has 3 billion cells that beat in synchronization to pump

more than 7,500 liters of blood each day through 100,000 miles of

blood vessels. It is a marvel of engineering, but it is also

notoriously poor at repairing itself.

Worldwide, 22 million people live with heart troubles, and researchers

have been hunting for ways to heal cardiac tissue. Some have tried

injecting cardiac stem cells directly into the site of damage (see

" Cells mend damaged mouse hearts " ). Others have engineered small

sheets of tissue that can patch damaged regions of the heart.

But the size of those cardiac patches has been limited. Although

existing blood vessels may feed thin slices of tissue, they are unable

to sustain thick patches or complex structures.

" It's a long way to go before you can regenerate the heart, " says

Gordana Vunjak-Novakovic, a bioengineer at Columbia University in New

York. " It's just too complex. " Finding a scaffold that could support

regeneration would solve a key problem in the field, she says.

From little seeds

" It looks like a ghost heart. And it feels a little like jello. "

Doris

Doris , a bioengineer at the University of Minnesota in

Minneapolis, and her colleagues decided that rather than manufacturing

a scaffold they would get one from nature. They pumped detergent

through the vasculature of rat hearts, stripping away the cells.

Twelve hours later, the cells were gone, leaving behind blood vessels

embedded in a mixture of collagen and other compounds that comprise

the 'extracellular matrix'.

" If you think about a steak, it's the gristle. It's the stuff

underneath the cells that holds the cells together, " says . " It

looks like a ghost heart. And it feels a little like jello. " The

gelatinous structure was found to have mechanical properties similar

to an intact heart, including its ability to spring back after stretching.

and her colleagues maintained the ghost heart in a special

bioreactor, and then 'reseeded' it by injecting it with heart cells

from newborn mice. The transplanted cells re-lined the blood vessels

and, three days later, began to beat with tiny, microscopic

contractions in response to an electrical current.

A few days after that, the contractions were visible to the naked eye

and the heart was pumping at 2% of its normal function. The results

are published today in Nature Medicine 1.

Pump it

Two percent may seem small, but it is a significant achievement,

observers say. " The fact that there is any contractile function after

going through what this thing went through is pretty amazing, " says

ph Vacanti, a surgeon and tissue engineer at Massachusetts General

Hospital in Boston who was not affiliated with the work.

Vacanti notes that getting heart function above just 10% would be an

improvement for some patients. Meanwhile, says there is plenty

of room for improvement in the ghost-heart method. " We haven't tried

to push the system yet, " says . " We wanted to see if this was

just some crazy idea. "

Some `decellularized' products are already used in humans. Pig heart

valves, for example, are transplanted into people after first being

cleaned of their cells. " It's less bizarre than it may look at first, "

says Vunjak-Novakovic.

Bare brains

and her collaborators have also applied the technique to

mammalian muscle, livers, kidneys and lungs, all with promising

results, she says. " The only organ that we've come across that doesn't

seem amenable to this is the brain, " says . " It turned more to

mush and did not hold up as well. "

It isn't yet known if donor scaffolds will be accepted by the

patient's immune system, but if cells used to re-seed the heart can be

taken from the recipient, the odds of rejection may be diminished. It

is also possible, adds Vacanti, that those host cells would gradually

replace the foreign extracellular matrix with their own material.

" It sounds like science fiction, " says . " But then in

retrospect, you think, `duh. It's kind of simple'. "

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