http://www.wired.com/news/technology/medtech/0,71817-0.html?tw=rss.index
Grow Your Own Limbs
By Kristen Philipkoski
In response to the hundreds of soldiers coming home from war with missing
arms or legs, Darpa is spending millions of dollars to help scientists
learn how people might one day regenerate their own limbs.
Prosthetics are getting better all the time, but they will never be as
good as the limbs we were born with. So two teams of scientists at 10
institutions across the country are competing to regrow the first
mammalian limb.
The two groups are sharing $7.6 million in grants for a year to find a way
to give humans salamander-like abilities. According to Army Medical
Command, 411 soldiers who fought in Iraq and 37 in Afghanistan are
amputees as a result of combat wounds. If preliminary research is
successful, the scientists could receive more funding for up to four years.
The researchers' first milestone is to generate a blastema - a mass of
cells able to develop into various organs or body parts - in a mammal.
"We have to show we can do that in a mammal by 24 months - and by 48
months we have to show that we can actually regrow digits," said Stephen
Badylak, director of the Center for Pre-Clinical Tissue Engineering at the
University of Pittsburgh's McGowan Institute for Regenerative Medicine,
and a principal investigator for his team. "This is really a Star
Wars-type project."
Mammals can't naturally regenerate limbs or digits beyond the fetal stage.
Amphibians like salamanders and newts, however, can regrow limbs, eyes and
even spinal cords. So the scientists are on a hunt for the molecular
signals responsible for controlling that regenerative ability.
"We're looking for what genes get turned on and off to make one
regenerative and one not," Badylak said. "We can regenerate as a fetus. We
know the potential is there, but it's a matter of unlocking that potential
(in adults)."
Badylak's team is working with a remarkably regenerative mammal - a mouse
discovered by accident in 1998.
Ellen Heber-Katz, a professor at the Wistar Institute in Philadelphia, was
working with mice that had been genetically engineered to develop lupus
when she noticed that some of their ears looked weird. She had punched
holes in them so she could separate her control from her treatment groups
in an experiment. But the holes quickly grew shut without a trace - not
even a hint of a scar.
The missing ear holes confused her research at the time, but the
phenomenon launched a whole new career for Katz.
She and her colleagues wanted to find out if other parts of these mice,
known as the MRL strain, would also regenerate. So they performed some
tests: They snipped off the tip of a tail, severed a spinal cord, injured
the optic nerve and damaged various internal organs.
All of the injuries healed, even the severed spinal cord. The results
caused Heber-Katz to shift her research from autoimmune disease to
regenerative medicine.
Now, thanks to Darpa's call for grant applications in regeneration,
scientists all over the country from various disciplines are working
together on the MRL mouse.
"It's an interdisciplinary team of people who would never otherwise work
together," Badylak said. "That's what Darpa does."
Hans Georg-Simon has been studying salamanders for 15 years. As part of
the Darpa project, he's identifying genes that control regeneration in
salamanders. If those same genes are active in the MRL mouse, he'll have a
lead on which genes in humans might be manipulated to allow regeneration.
At some point during evolution, humans seem to have lost the ability to
regenerate, Simon said.
"There are actually more species on this globe that can replace lost
structures during regeneration than there are animals who can't," he said.
"From a human perspective, we always think we are the masters; we know
everything. But no, it is not so. We belong to the species
that have
secondarily lost the ability to regrow lost tissues."
Another salamander scientist, Ken Muneoka, a professor at Tulane, is on
the competing team. His lab is focusing on a type of cell called
fibroblasts. The cells exist throughout the body and produce collagen
fibers.
"In salamanders we have pretty good evidence that these cells control
spatial information in the body, that is to say where a cell or tissue is
located," Muneoka said.
Fibroblasts in mammals invade wounds and create scar tissue. "In mammals
(fibroblasts are) not doing what we want them to do," he said. "We want to
redirect their activity in response to injury."
And now for the most annoying, but necessary, question a reporter can ask
a scientist: When will you get this to work in humans?
"It's impossible to know," Muneoka said. "I could tell you next year or 20
years. It has a lot to do with discovery. We might find out that if we
just alter one gene pathway in a mammal
all of a sudden cells (act) like
a salamander. That would be spectacular, but I don't think so. I think
it's going to require lot of small changes. So it will take a lot of time
to discover them."
Simon also believes the discovery process will be a long one, up to 20
years. "But dont hold me to that," he said. "I would not give you my left
arm for that."
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