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The Raelian Movement
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A Limb Regeneration Mystery Solved
http://www.technologyreview.com/biomedicine/22955/?nlid=2147
Salamanders regrow limbs with less drastic cellular changes than
previously thought.
By Courtney Humphries
Thursday, July 02, 2009


Salamanders have an enviable ability to regrow appendages that are
amputated or injured; they re-create all the bones, muscle, skin,
blood vessels, and nerves of the new body part so adeptly that it's
hard to tell that it was ever missing. Because of this ability,
salamanders have been popular subjects for scientists studying
regeneration--and trying to learn how human cells might be coaxed to
perform the same feat.

In salamanders, new tissues come from a tumorlike mass of cells that
forms at the site of the injury, called the blastema. Until now, most
scientists thought that the blastema contained a population of stem
cells that had become pluripotent--capable of giving rise to all the
needed tissues. But a new paper in the journal Nature provides
evidence that this is not the case. Instead, stem cells involved in
regeneration only create cells of the tissue that they came from. The
finding suggests that regeneration does not require cells to reprogram
themselves as dramatically as scientists had assumed.

Elly Tanaka, lead scientist of the study at the Center for
Regenerative Therapies, in Dresden, Germany, says that "a lot of
people had the impression that these blastema cells were all the
same." Tanaka's lab had even shown previously that a single muscle
fiber could give rise to several types of cells in a regenerated limb.
But previous studies, she says, relied on imperfect methods of
tracking cells, such as using fluorescent dyes that may have leaked
out to other cells.

In the latest study, Tanaka's team employed a novel method for
tracking the fate of cells from different tissues in a type of
salamander called the axolotl. The researchers first created
transgenic axolotls that carried green fluorescent protein (GFP) in
their entire bodies. When the animals were still embryos, the
researchers removed a piece of tissue from the limb region of the
transgenic animals and transplanted the tissue into the same location
in nontransgenic axolotls. The transplants were incorporated into the
growing body as normal cells, and when the limb of the transplant
recipients were then severed, the researchers could track the fate of
the fluorescent cells as the limb regrew.

The researchers used this method to track the fate of cells of the
inner and outer skin, muscles, and cartilage, as well as Shwann cells,
which insulate nerve fibers. They found that, contrary to previous
evidence, muscle cells at the amputation site only become muscle cells
in the new limb. Other cell types also stuck to their previous
identities; the only exception, Tanaka says, is that cells of the
inner layers of skin and cartilage seem to be able to transform into
one another. But for the most part, she says, the blastema is not a
homogeneous mass of cells but "a mix of stem or progenitor cells from
different tissues that stay separate during the whole process."

The researchers also found that some cells remember not only their
identities but also their position in the body. Cartilage cells, for
instance, remember if they are supposed to form an upper arm, lower
arm, or hand, while Shwann cells simply migrate anyplace that they are
needed.

Tanaka says that the finding will provoke a major shift in thinking
about the requirements of regeneration. In explaining why salamanders
can regrow limbs and humans can't, she says, "the hypothesis was that
it's because salamanders can powerfully alter the identity of cells."
But in fact, their cells never really lose their identities; instead,
they seem to use tissue-specific stem cells capable of generating a
certain part of the new limb. Tanaka points out that humans also have
tissue-specific stem cells that replace different kinds of tissue.
Perhaps salamanders "are not doing something much more complicated
than what human stem cells would do," she says. Coaxing human cells to
regenerate might not require steps as drastic as making cells
pluripotent.

Alejandro Sánchez Alvarado, a scientist who studies regeneration at
the University of Utah School of Medicine, says that this method of
"tattooing" the transplanted cells genetically is "a novel technique
for the field of regeneration." Tanaka believes that previous studies
may have misled researchers by using imperfect tracking methods such
as dyes by culturing cells before transplanting them and possibly
altering them, or by allowing different cell types to contaminate
samples.

Sánchez also says that the idea that blastemas held several different
cell types was a "minority hypothesis" and that this study "shows that
this hypothesis turns out to be correct." He cautions that scientists
now need to determine whether this phenomenon is the same in adult
axolotls and in newts, which are a primary model organism for
regeneration studies. But if the same mechanism turns out to underlie
other cases of regeneration, it would change what scientists believe
is required to regrow body parts, Sánchez says. But it leaves a major
question unanswered: if humans already have tissue-specific stem
cells, what exactly is the difference between our cells and those of
salamanders?