Researchers discover mechanism for
multiplying adult stem cells
CAMBRIDGE, Mass. (May 5, 2005) — While the field
of human embryonic stem cell research receives a tremendous
amount of public attention, many scientists are also
exploring the potential of adult stem cells for possible
therapies. But this field raises other difficulties.
Although adult stem cell research isn’t fraught
with the controversies that surround embryonic stem
cells, adult stem cells are extremely difficult to isolate
and then to multiply in a lab dish. Now, as reported
in the May 6 issue of the journal Cell, researchers
in the lab of Whitehead Institute Member Rudolf
Jaenisch have discovered a mechanism that might
enable scientists to multiply adult stem cells quickly
and efficiently.
“These findings provide us with a new way of
looking at adult stem cells and for possibly exploiting
their therapeutic potential,” says Jaenisch, who
also is a professor of biology at MIT.
This research focuses on a gene called Oct4, a molecule
that is known to be active in the early embryonic stage
of an organism. Oct4’s primary function is to
keep an embryo in an immature state. It acts as a gatekeeper,
preventing the cells in the embryo from differentiating
into tissue-specific cells. While Oct4 is operating,
all the cells in the embryo remain identical, but when
Oct4 shuts off, the cells begin growing into, say, heart
or liver tissue.
Konrad Hochedlinger, a post-doctoral researcher in
Jaenisch’s lab, was experimenting with the Oct4
gene, curious to see what happens in laboratory mice
when the gene is reactivated in adult tissue where it
has long been dormant. Hochedlinger found that when
he switched the gene on, the mice immediately formed
tumors in the gut and in the skin where the gene was
active. When he switched the gene off, the tumors subsided,
demonstrating that the process is reversible.
Discovering that simply flipping a single gene on and
off has such an immediate effect on a tumor was unexpected,
even though Oct4 is known to be active in certain forms
of testicular and ovarian cancer. Still, the most provocative
finding was that “Oct4 causes tumors by preventing
adult stem cells in these tissues from differentiating,”
says Hochedlinger. In other words, with Oct4 active,
the stem cells could replicate themselves indefinitely,
but could not produce mature tissue.
One of the main obstacles with adult stem cell research
is that, in order for these cells to be therapeutically
useful, researchers need to multiply them in the lab.
But when adult stem cells are isolated, they immediately
start growing into their designated tissue type. It
would be ideal if scientists had a way to take a liver
adult stem cell and multiply it in a dish without having
it form mature liver tissue.
This experiment showed that when Oct4 was reactivated,
the adult stem cells in those tissues continued to replicate
without forming mature tissue. In a mammal’s body,
this type of cell behavior causes tumors. But under
the right laboratory conditions, it could be a powerful
tool.
“This may allow you to expand adult stem cells
for therapy,” observes Hochedlinger. “For
instance, you could remove a person’s skin tissue,
put it in a dish, isolate the skin stem cells, then
subject it to an environment that activates Oct4. This
would cause the cells to multiply yet remain in their
stem cell state. And because this process is reversible,
after you have a critical mass of these cells, you can
then place them back into the person where they would
grow into healthy tissue.”
“This could be very beneficial for burn victims,”
Jaenisch adds.
Researchers in his lab are also exploring whether activating
Oct4 in somatic cells, such as skin cells, would make
it easier for these cells to be reprogrammed when used
as donors for nuclear transplantation. If so, it may
help scientists more efficiently “customize”
embryonic stem cells that could be used to treat diseases
such as diabetes or Parkinson’s.
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