Patches for a Broken Heart
Patches for a Broken Heart Using a space-age device called
a bioreactor, researchers have grown patches of tissue that beat
and respond much like a human heart does.
February 14, 2002: Â Thump-thump, thump-thump. There's nothing more reassuring than the cadence of a healthy beating heart. It's the first thing your doctor listens for when you go in for a check-up.
Gurgles, swishes, and hiccups, on the other hand, are worrisome. They are the tell-tale sounds of imperfect or diseased hearts. Millions of Americans have hearts that don't work as they should; indeed, heart disease is the single leading cause of death in the United States.
One day, perhaps, biomedical engineers will simply grow new hearts for people who need them, using cells taken from the patients themselves as seeds. Such hearts would be young, alive, and welcomed by the immune systems of their recipients.
It's a far-off goal, but some researchers are already making progress. Among them are MIT scientists Lisa E. Freed and Gordana Vunjak-Novakovic. The pair have used a NASA-designed device called "the bioreactor" to grow tiny patches of heart tissue -- patches that beat much like a healthy human heart.
"It's the most exciting thing to see these tissues contract," says Freed, with enthusiasm. "Everybody loves to watch them." The tissue contracts all together, she says, in a synchronous way, exactly like a beating heart. The tissue itself is tan, and it's kept in a red liquid that looks like Hawaiian punch.
Left: MIT Scientist Lisa Freed poses with the NASA bioreactor in the foreground. Image credit: D. Coveney, MIT.
NASA developed the bioreactor for cell studies in space. It is a soup-can-sized chamber that slowly turns. Fluid within it delivers oxygen to cells and wafts away their wastes without vigorous stirring that might rip apart tissues and cell clusters.
Back on Earth scientists discovered that the bioreactor mimicked some aspects of weightlessness. Cell clusters inside the bioreactor continually fall yet never hit bottom -- much like freely-falling spacecraft that orbit our planet. In Earth-labs, cells are most often grown in petri dishes, where they settle in a flat layer at the bottom. But in the bioreactor, floating cells can easily gather into 3-dimensional structures that resemble real tissues and organs in the human body.
The recipe for growing a patch of heart tissue in the bioreactor begins with 5 million or so individual heart cells. To function as tissue, those cells need to form mutual connections known as gap junctions, which allow them to exchange electrical signals. The ability of cardiac cells to transfer such signals is what allows the heart to contract, or beat. "Cells like to be connected with each other," notes Freed. In a close, nutrient-filled environment like the bioreactor they will try to form gap junctions on their own.
Freed and colleagues guide the process with the aid of a scaffold: a three-dimensional structure on which the cells can gather. "We've found that the best scaffolds look like textiles," says Freed. They're made of fibers 10 or 15 microns in diameter (about the same size as the cells), and these fibers are linked into a fabric or a mesh.
Right: A scanning electron micrograph image of biodegradable scaffolding. Credit: L. Freed, G. Vunjak-Novakovic, MIT
The scaffold is constructed of biodegradable materials like the polymer used in absorbable surgical stitches. After the tissues have formed (in the 3-D shape defined by the scaffold) the underlying scaffold simply dissolves.
Cardiac cells are sensitive to their growth environment, notes Freed. They require lots of oxygen. In the human heart each cell is within 20 micrometers of a blood vessel, which brings it oxygen. But there are no blood vessels in bioreactor-grown tissue -- not yet anyway. Instead, the bioreactor's circulating fluids must deliver any oxygen the cells need.
Below: A patch of bioreactor-grown heart tissue. Credit: L. Freed, G. Vunjak-Novakovic, MIT
It takes about one week for the bioreactor to produce a patch of tissue five millimeters in diameter and a mere tenth of a millimeter thick. Like real heart tissue, these patches beat spontaneously. "They'll pick a rate and they'll beat at it," says Freed. "If you blow on them, they'll change." They're very sensitive to stimulation, she says. "If they warm up or cool down, if someone slams the door, their rate can change."
Freed, Vunjak-Novakovic, and collaborators hope to improve the tissue by making it thicker. To do this, says Freed, they'll need to develop tiny conduits -- like blood vessels -- that can supply nutrients and oxygen to cells trapped in the inner tissue mass. She and other researchers have begun to culture heart cells and blood vessel cells together, but they haven't yet succeeded in coaxing blood vessels to form. More work is needed.
Eventually lab-grown cardiac tissue could be used to repair heart defects or to replace tissue damaged in a heart attack. That, though, is still in the future. A more immediate use might be to test pharmaceuticals: New drugs are typically tested on monolayers of cells grown in petri dishes. But, Freed points out, such tests "might not [reveal all the] good effects or bad effects, simply because [cells grown in petri dishes] are not a good model system for heart tissue..." Testing drugs using a bioreactor-grown heart tissue might yield more realistic results.
Right: Cells grown in petri dishes on Earth lie flat at the bottom of the dish. In space or in the bioreactor, floating cells can form 3-dimensional structures. Image credit: Dave Dooling.
The ultimate goal is to grow replacement body parts -- and not only hearts. Cartilage, liver, prostate and kidney tissues have also been produced in a bioreactor. The possibilities are breathtaking ... yet distant. There's much to be done and many years of research lie ahead.
Even so, a quarter-inch disk of beating heart is a very exciting start.
NASA's Office of Biological and Physical Research supports studies of the human body in space.
Scientists grow heart tissue in Bioreactor -- (Science@NASA) If you've ever seen a pile of ivy that has taken the shape of an old barn that it has overgrown, you've seen the principle that researchers are following in trying to grow replacement parts for bodies.
More bioreactor links: Bioreactor expands health research (Science@NASA); Bioreactor research (MSFC); Advancing Heart Research (Microgravity News); Dr. Neal Pellis' testimony to the House Subcommittee on Space (house.gov)
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