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Off-the-shelf replacements

It was not the goal of her research, but Pamela C. Yelick recounts with some small pride how her recent breakthrough in growing replacement teeth using tissue engineering became fodder for one-liners on "Saturday Night Live" and other late-night shows.

Yelick, an investigator at the Forsyth Institute in Boston, tooks cells from the teeth of six-month-old pigs and embedded them in a special polymer structure. Then, the living structures were implanted in the abdomens of rats. (Insert punch line here.)

Aside from generating chuckles, the experiment broke new ground in the quest to replace lost teeth with real replacements instead of dentures. After 30 weeks in the host animals, the cells had grown tooth crowns that contained dentin, the bony substance that makes up most of teeth, a pulp chamber, and an organ to generate enamel, the hard, shiny substance that coats a tooth. "We're estimating that within seven to 10 years, we'll have a living tooth that can be tested in human clinical trials," Yelick said. "Along the way, there might be other things that might happen sooner than a whole tooth, bioengineered roots that supported false teeth in the jaw and could respond to pressure from your bite."

The tooth experiment illustrates the promise and the frustration of tissue engineering. It is a rapidly emerging field, growing living tissues to replace damaged or diseased parts of the body.

Scientists are making dramatic progress in learning how to grow functional tissues, but the ultimate goal -- off-the-shelf or grown-on-demand replacements that can keep patients alive after vital organs fail -- remains tantalizingly far off.

James R. Hall, a biotech industry consultant with Wood Mackenzie, says the results so far are limited.

"The science fiction view was we could grow tissue and organs and have an inventory of replacement parts as people grow older," said Hall. "The reality is: At this point, it's more applicable to more mundane procedures, such as replacement skin."

But a bevy of local scientists and researchers are working to change that, attacking the problem with two new technologies.

The first approach is the use of stem cells, the tiny, undifferentiated cells found in embryos that have the ability to develop into any type of tissue within the body. Scientists have also found stem cells in adult animals and in other sources, such as the umbilical cord blood of newborns. These alternative sources provide stem cells with many of the same pluripotent development possibilities, but do not raise the ethical issues surrounding harvesting cells from embryos for therapeutic purposes.

Tissue engineers are focused on stem cells not only because they have the ability to develop into many types of tissue, but because they send signals to each other that guide the growing tissue to develop into a cohesive organ.

Yelick's work was particularly exciting because it postulated the existence of never-before-seen dental stem cells.

The second approach is the use of nanotechnology, the science of making and manipulating tiny structures.

For years, researchers have developed ways of seeding underlying structures, often called scaffolds, with cells that could proliferate and turn into tissue. Remember the creepy photo a few years ago of the mouse with the human ear growing on its back? The organ developed on an underlying scaffold of polymer, seeded with cartilage cells. Once implanted on the mouse, a network of blood vessels developed and kept the tissue alive. Such polymers are designed to degrade, leaving only the new tissue.

But as researchers learned to grow tissues, the new challenge became supplying each of the cells with an adequate blood supply. Dr. Joseph Vacanti of Massachusetts General Hospital, the man responsible for that ear, and Robert Langer of Massachusetts Institute of Technology saw a possible solution in the ubiquitous computer chip.

The chips that make up the brains of computers and other electronic devices include millions of tiny electrical pathways imprinted on the silicon substrate. The same methods, Vacanti and Langer thought, could be used to create polymer scaffolds with a built-in pattern of tiny blood vessels.

"The body has done a beautiful job of microfabrication," said Langer, a professor of chemical and biomedical engineering. "The question is, how can we recreate it?"

Both are now working with Jeff Borenstein, director of the Biomedical Engineering Center at the Charles Stark Draper Laboratory in Cambridge. The lab helped design microelectronic mechanical systems that are used as sensors, such as the chip-based accelerometers used to trigger automobile air bags.

The surprise, Borenstein said, is that the techniques of building electronic devices were so readily adaptable to biological challenges. "We're able to use the same molding and casting techniques to build the structures for biomedicine, but we're using polymers instead of silicon," said Borenstein. "It's basically a translation of an existing platform."

Beginning with a real liver, Borenstein used a liquid polymer to make a 3-D model of its internal blood vessels. Then the model is cut into thousands of tiny slices, each one of which can be replicated using microscopic molding.

"In order to build real, functioning organs, we're going to have to stack hundreds of those layers," Borenstein said. "There's a convergence of microtechnology, microfabrication, and living cells and tissues."

The tissue engineering work is being coordinated by the Center for the Integration of Medicine and Technology, a consortium of Harvard's teaching hospitals, MIT, and Draper. The group's ambitious goal for 2008: to have tissue-engineered livers and kidneys implanted and working in animals.

Vacanti, the head of the center's tissue engineering program, makes it sound as though it's within reach.

"We have proof of principal that all the concepts appear correct and the devices made using this technology work and keep the cells of the organ alive and functioning in culture," he said. "We're doing our first animal studies."

Jonathan Rosen, director of the center's Office of Technology Implementation, is also optimistic. "We're within a decade of human clinical trails with a replacement organ," he said. "It's not just a dream or a concept anymore. We're within range."

Jeffrey Krasner can be reached at

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