How to Build a Body Part

By Josh Fischman

There's a human liver sitting in a lab dish in Madison, Wis. Also a heart, a brain and every bone in the human body--even though the contents of the dish are a few cells too small to be seen without a microscope. But these are stem cells, the most immature human cells ever discovered, taken from embryos before they had decided upon their career path in the body. If scientists could only figure out how to give them just the right kick in just the right direction, each could become a liver, a heart, a brain or a bone. When a team from the University of Wisconsin announced their discovery last fall, doctors around the world looked forward to a new era of medicine--one without organ-donor shortages or the tissue-rejection problems that bedevil transplant patients today.

Doctors also saw obstacles, though. One of them was a U.S. Congress skittish about research on stem cells taken from unwanted human embryos and aborted fetuses. Indeed, last week 70 lawmakers asked in a firmly worded letter that the Federal Government ban all such work.

Yet the era of "grow your own" organs is already upon us, as researchers have sidestepped the stem-cell controversy by making clever use of ordinary cells. Today a machinist in Massachusetts is using his own cells to grow a new thumb after he lost part of his in an accident. A teenager born without half of his chest wall is growing a new cage of bone and cartilage within his chest cavity. Scientists announced last month that bladders, grown from bladder cells in a lab, have been implanted in dogs and are working. Meanwhile, patches of skin, the first "tissue-engineered" organ to be approved by the U.S. Food and Drug Administration, are healing sores and skin ulcers on hundreds of patients across the U.S.

How have scientists managed to do all this without those protean stem cells? Part of the answer is smart engineering. Using materials such as polymers with pores no wider than a toothbrush bristle, researchers have learned to sculpt scaffolds in shapes into which cells can settle. The other part of the answer is just plain cell biology. Scientists have discovered that they don't have to teach old cells new tricks; given the right framework and the right nutrients, cells will organize themselves into real tissues as the scaffolds dissolve. "I'm a great believer in the cells. They're not just lying there, looking stupidly at each other," says Francois Auger, an infectious-disease specialist and builder of artificial blood vessels at Laval University in Quebec City. "They will do the work for you if you treat them right."

FLESH AND BONES. Treating bone cells right is what Charles Vacanti, an anesthesiologist and director of the Center for Tissue Engineering, has been doing at the University of Massachusetts Medical Center in Worcester. When that machinist lopped off the top of his thumb, Vacanti took some of the victim's bone cells, grew them in the lab and then injected them into a piece of coral fashioned into the shape of the missing digit. "Coral's got lots of interconnected channels for the bone cells to grow in," says Vacanti. It also degrades as bone replaces it. The patch was implanted back on the thumb a few months ago. "It looks like he's growing good bone," Vacanti reports. "He could get most of his function back."

Moving from the thumb to other hand parts, Charles' brother Joseph Vacanti, a transplant surgeon and tissue-engineering pioneer in his own right, has grown human-shaped fingers on the back of a mouse, demonstrating that different cell types can grow together. He and colleagues at Boston's Massachusetts General Hospital shaped a polymer to resemble the end and middle finger bones. These shapes were seeded with bone, cartilage and tendon cells from a cow. Then the medical team assembled the pieces under the skin of the mouse--"just like you'd assemble the parts of a model airplane," says Vacanti.

VEINS AND ARTERIES. Blood vessels present a special challenge: they must be strong yet flexible enough to expand and contract with each heartbeat. Joseph Vacanti's group has grown a tube of sheep-muscle cells around a polymer, added closely packed lining cells to the inside and stitched it into a sheep's pulmonary-artery circuit. Blood pulsing against the walls gradually strengthens the muscle cells, just as weight training builds biceps. To make smaller vessels, Laval's Auger bends a sheet of muscle cells around a plastic tube and reinforces it with an outer layer of stiffer cells. Then he removes the tube and seeds the inside with lining cells, which soon grow together. The vessels have worked well in animal tests, and in the lab have withstood blood pressure 20 times normal.

LIVERS AND BLADDERS. Anthony Atala, a surgeon who makes bladders at Boston's Children's Hospital, has taken muscle cells from the outside of dog bladders and lining cells from the inside and grown them in his lab. The cells, fed the proper growth-prompting chemicals, happily go forth and multiply. "In six weeks we have enough cells to cover a football field," Atala says. He placed a few muscle cells on the surface of a small polymer sphere and some lining cells on the inside. When he inserted the sphere in a dog's urinary system, the artificial bladder began to function like the real thing. Bioengineer Linda Griffith at nearby Massachusetts Institute of Technology is doing similar work with rat-liver tissue.

THE HEART--AND BEYOND. One drawback with all these techniques is that it takes time, usually several weeks, to grow organs using the patient's own cells. Although using these cells sidesteps the rejection problem, time is a luxury many patients, particularly heart patients, can't afford. So Michael Sefton, who directs the tissue-engineering center at the University of Toronto, has proposed building a "heart in a box"--complete with chambers, valves and heart muscles--from cells genetically engineered to block the signal with which the body marshals cells to attack invaders. Sefton envisions spin-offs along the way--like immune-system-resistant replacement valves--to justify the project's $5 billion cost.

Replacement hearts--or even replacement heart parts--are at least a decade off, estimates Kiki Hellman, who monitors tissue-engineering efforts for the FDA. "Any problem that requires lots of cell types 'talking' to one another is really hard," she notes. Bone and cartilage efforts are much closer to fruition, and could be ready for human trials within two years. And what of those magical stem cells that can grow into any organ you happen to need--if the law, and biologists' knowledge, permit? "Using them," says Sefton, "is really the Holy Grail."