AR-News: (US) TISSUE ENGINEERING:Off-the-shelf replacements

[Masako Miyaji]

http://www.boston.com/business/globe/articles/2004/02/23/off_the_shelf_replacements/

TISSUE ENGINEERING 
Off-the-shelf replacements
By Jeffrey Krasner, Globe Staff, 2/23/2004

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 krasner at globe.com.

© Copyright 2004 Globe Newspaper Company.


__________________________________
Do you Yahoo!?
Yahoo! Mail SpamGuard - Read only the mail you want.
http://antispam.yahoo.com/tools