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any number of diseases, this technique
could one day provide new treatments,
from swapping out neurons in Parkinson’s disease patients to pumping up the
number of insulin-producing pancreatic
cells in diabetics.
But, Wernig says, some technical hurdles must be overcome before these cells
could be used for such transplants. Until
then, induced neurons made from patients
with any of various genetic diseases could
almost immediately help scientists learn
how such diseases develop and can be
used to test new drugs. Researchers are
already working out ways to make a variety of cell types from induced pluripotent
stem cells, but the new technique is faster
and more efficient, Wernig says.
The majority of induced neurons created by the team behaved just like regular neurons, communicating with other
neurons in the lab dish and making proteins. But the researchers don’t yet know
whether the cells’ DNA carries normal
chemical signatures, known as epigenetic
marks, that usually help prevent cells from
changing jobs. When altered, these marks
can sometimes lead to cancer.
But other scientists are excited about
the prospect of such transformations
occurring in the body. “If it’s a naturally
occurring repair mechanism, that could
be exciting,” says Paul Sanberg, a neuro-
scientist at the University of South Flor-
ida College of Medicine in Tampa. If such
conversions happen naturally, scientists
may be able to figure out ways to get the
body to heal itself rather than
having to transplant cells.
After a stroke, for instance,
brain cells known as glia rush
to the injury site and multi-
ply themselves. Glia might be
coaxed to transform into neu-
rons and repair the damage.
Because the scientists had
to genetically engineer the
mouse skin cells to make
the neuron-inducing transcription fac-
tors, the technology probably won’t pro-
duce cells for transplant any time soon,
Sanberg says. “Once you put in genes,
it makes it a little more difficult to use
clinically,” he says. Inserting genes might
cause cancer-promoting mutations,
for example, so scientists may need to
develop alternate approaches that would
turn on the same transcription factors
chemically instead of genetically. s
“If it’s a
naturally
occurring
repair
mechanism,
that could be
exciting.”
Scientists already know that some
cells in the body change identities in a
type of disease known as metaplasia. For
example, cigarette smoking can change
some cells that line the lungs into related
skinlike cells, and reflux disease may
alter cells in the esophagus
to become another type of
cell, Wernig says. The minor
job switches help cells withstand the stress of smoke or
stomach acid.
Researchers have thought
that major changes, such as
skin cells becoming neurons, were nearly impossible
unless the epigenetic slate
was wiped clean, as it is with induced
pluripotent stem cells. Such big alterations might cause serious diseases if
they happen willy-nilly. “It’s actually a
bit scary to think it’s so easy to turn skin
cells into neurons because that’s not
something you want to happen in your
body,” Wernig says.
PAUL SANBERG
1962 DNA-carrying nucleus from an adult
frog’s intestinal cell is transplanted into an
egg, producing a new frog
1981 Embryonic stem cells are cultured
from mouse embryos and grown into a mouse
1996 Dolly the Sheep (left) is cloned, showing that mammalian adult cells can be repro-grammed
1998 Embryonic stem cells are isolated
from human blastocysts (one shown, top right)
2006 Scientists use transcription factors
to induce mouse cells to become pluripotent
(induced pluripotent mouse cells shown)
2007 Teams reprogram adult human skin
cells to an embryonic-like state
2008 Pancreatic cells in mice are turned
directly into related insulin-producing cells
