The November news that two groups
of scientists have zapped skin cells into stem cells
has launched a media frenzy and a flurry of public excitement.
The studies — one from Japan, appearing in the
November 30 issue of Cell, and one out of Wisconsin
in the December 31 Science — raise hope
that embryonic stem cells may no longer be needed for
stem cell research, but some experts say reports of
a stem cell revolution are overstated.
The excited politicians and ethics
groups who believe this research means an end to the
embryonic stem cell debate that's plagued American research
in recent years should stem their enthusiasm, say researchers.
(After the two studies entered the news cycle even the
White House hopped on the bandwagon, crediting President
Bush with inspiring the research.) Some scientists fear
the hype surrounding the two studies could send embryonic
stem cell research back to the stone age. "We still
need to study embryonic stem cells," says Sophie Chargé,
PhD, the director of scientific programs at Canada's
Stem Cell Network. "These studies are great. They provide
clear evidence that we can use adult cells to create
pluripotent stem cells, but we still need to know how
they behave and what they do."
POTENT
FINDINGS
The teams used different methods and different types
of skin cells to get these scientific shape-shifters:
the Japanese study used cells from the face of a 36-year-old,
and the Wisconsin group used cells from the foreskin
of an infant.
Scientists in both studies isolated
four genes that could turn a normal adult cell into
something resembling an embryonic stem cell. They then
took those four genes, put them in a retrovirus and
used the virus to introduce them into adult cells, making
them pluripotent and able to proliferate indefinitely.
So can these induced stem cells really do everything
embryonic stem cells do?
Embryonic stem cells are pluripotent:
they can turn into any of the 220 types of cells in
the human body, from heart cells to nerve cells. Ditto
for the induced cells.
Embryonic stem cells can proliferate
like crazy, so just a few cells can generate entire
cell lines and multiply almost indefinitely. Same with
the induced ones, say the researchers.
But not everything's the same.
The Japanese team found genetic differences between
the induced pluripotent stem (iPS) cells and embryonic
stem cells, which means it's too early to tell if they'll
behave the same way in a clinical use, both teams agree.
And only two of the genes used
in the retroviruses were common to both studies, raising
the possibility of other genes' involvement in embryonic
stem cell development. "These studies show that if you
have the right combination of four genes, you can get
cells to become pluripotent and proliferate. But there
are potentially six genes involved in this process at
least," says Dr Chargé. And exactly how four
out of those six genes work is still a mystery.
POTENTIAL
PROBLEMS
Beyond the unknown genetic entities, the very use of
a retrovirus raises concerns. "There are potential problems
to having a retrovirus in the cell," says Dr Chargé.
"You can induce a mutation when you put the DNA sequence
into the cell's DNA, which could cause cancer. Or if
the cell already has an oncogene and you make it pluripotent
and able to proliferate, then you'll also end up with
cancer."
Another concern, according to the
Japanese team, is that only a small fraction of the
skin cells turned into iPS cells. That means that where
the virus inserts the genes in the cells' DNA may be
vital. And figuring out how to plug them into the right
spot is still an open question.
FUTURE
APPLICATIONS
But even with those issues to contend with, the iPS
cells have tremendous potential for lab use. They may
be useful in testing drugs, says the Japanese report.
Scientists, for instance, can use liver cells to make
iPS cells and then test new drug candidates on them
to see if the drugs would harm the liver.
The findings also open the door
to a new kind of personalized medicine, according to
Dr Chargé. "If a patient has a certain disease,
like Alzheimer's or Parkinson's for example, you can
take his skin cells, re-program them to become nerve
cells and implant them in his brain. And you know you
won't have a rejection problem, since they come from
the same person."
But that's still years away. "They
need to understand what are the pathways involved in
the transformation of these cells," says Dr Chargé.
"And they need to find ways to make it safer before
the technique can be used on humans."
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