Stem Cell Alchemy
Refined
By Brandon Keim
Wired Science
September 25, 2008
Scientists may have found a safer way of giving a flake of
skin the biologically alchemical powers of embryonic stem cells.
They turned adult cells into versatile, embryonic-like cells
without causing permanent damage -- potentially solving the central problem of
a promising but uncertain field of stem cell science.
"This is certainly a major stem cell milestone,"
said Advanced Cell Technologies chief scientific officer Bob Lanza, who was not involved in the research. "It’s the
first ray of light that iPS cells could soon be used
to treat patients."
These iPS cells -- short for
induced pluripotent stem cell -- debuted less than a
year ago: By using viruses to insert key developmental genes, researchers coaxed
human skin cells into an embryonic state, capable of growing into almost any
other type of tissue.
It was the biggest stem cell breakthrough in a decade. No
longer would tricky -- and ethically controversial -- manufacturing procedures
be required to produce ultra-versatile stem cells. Cloning wouldn't be needed
to produce personally customized embryonic stem cell lines, which remain as
elusive as they are promising.
But there was a catch: Viruses used to reset the cells
tended to fuse with their DNA, leading to unpredictable mutations and cancer.
The cells were promising in principle, but couldn't be used medically. The
standard iPS technique was a blunt and damaging instrument.
The new technique doesn't cause permanent genetic
alterations; it's a scalpel that leaves no scar behind. And though important
caveats remain -- the procedure, published today in Science, was performed on
mice -- it has made safe iPS cells a realistic
possibility.
"Clinical translation of iPS
technology has been dead in its tracks," said Lanza.
"The use of iPS cells to treat -- or even cure
-- human disease may not be far away."
To produce their iPS cells, the
researchers added cell-reprogramming genes to adenoviruses, a type of virus
that infects cells without affecting their DNA. The adenoviruses pumped out
cell-reprogramming proteins, turning the cells embryonic, and then departed.
"You produce proteins for a while, but over time -- with
cell division -- both DNA proteins are diluted out from the cell," said Konrad Hochedlinger, a
Hochedlinger's team grew the cells
into lung, brain and heart tissue -- benchmark measurements of versatility --
and used the cells to create mouse embryos, which they allowed to develop.
Those mice remained cancer-free for four months. That's not long enough to be
completely certain of their safety, but it's reassuring nonetheless.
"Some published reports on mice made with retrovirally produced iPS cells
succumbed to tumors as early as four weeks after birth," said Hochedlinger.
Old-fashioned iPS cells, said Lanza, would never have been safe enough for FDA approval.
But he warned that duplicating Hochedlinger's feat
"may be a challenge -- and far more difficult -- in the human
system."
Some politicians and bioethicists, including Republican
presidential candidate John McCain, have hoped that iPS
cells would soon make embryonic stem cell research unnecessary. But stem cell
scientists say it's too soon to compare embryonic stem cells, which have been
studied for more than a decade, with iPS cells. It's
also possible that both of types of cell, as well as adult stem cells, will provide
therapies that the other types cannot.
"There are still a lot of unknowns, and we cannot
afford to put all our eggs in one basket," said Lanza,
while Hochedlinger called embryonic stem cells the
"gold standard."
But the findings are still a testament to the rapidly
developing field of iPS research, which in less than
a year has gone from proof-of-principle to mouse therapies to the latest
refinement.
"I have never seen a field move forward as fast as this
one," said Hochedlinger.
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