Cellular conversion turns brain into blood
By J. Travis
Talk about a career change. The unspecialized cells that normally give rise
to the various cell types in the brain can also act as bone marrow, the crucial
source of an adult body's blood cells.
Scientists discovered this remarkable ability when they injected these
so-called neural stem cells into the blood of mice whose own bone marrow had
been almost completely destroyed by irradiation. The neural stem cells, whose
progeny were identifiable by means of a genetic marker previously slipped into
them, engrafted as normal bone marrow transplants do and began producing blood
cells.
"We really had a hard time convincing ourselves of our own data,"
notes Angelo L. Vescovi of the National Neurological Institute in Milan, Italy.
He, Christopher R.R. Bjornson of the University of Washington in Seattle, and
their colleagues describe the neural stem cell transplants in the Jan. 22
Science.
The experiments suggest that a cell's lot in life, usually determined during
the growth of an embryo, isn't as hard and fast as once thought. "Even
when a cell seems to have committed to a particular organ, there are still some
cells that can switch that fundamental identity. That's an intriguing biological
concept," says Evan Y. Snyder of Children's Hospital in Boston, who has
isolated human neural stems cells (SN: 11/7/98, p. 293).
Until recently, scientists assumed that most adult cells had made
irreversible commitments to a particular fate, becoming heart cells or liver
cells, for example. The cloning of Dolly the sheep and other animals from
various adult cells challenged that dogma, however. Still, those experiments
involved removing the genes of an adult cell and placing them into an egg, a
transfer that somehow reverted the genes to their embryonic state (SN: 4/5/97,
p. 214). In the new experiments, the researchers have shown that they can
directly change the role of some adult cells simply by placing them in a new
environment.
Vescovi notes that his unusual experiment was prompted in part by reports of
brain tumors that contained muscle cells in addition to brain cells. Those
cases hinted that brain cells could develop into very different cell types.
After injecting the neural stem cells into mice, the researchers showed that
the cells seeded the animals' bone marrow and spleens, which also produce new
blood cells. They also showed that individual white blood cells from the animals
had the genetic marker belonging to the neural stem cells.
Although the researchers are confident that the transplanted neural stem
cells produced new red blood cells, they haven't proved that point. Mature red
blood cells have no DNA-containing nuclei, making it impossible for the
investigators to detect the genetic marker used to label the neural stem cells
and their progeny.
Vescovi's team is now testing whether human neural stem cells can also act
as bone marrow when injected into mice. "If the principle holds for human
cells, we'd like to try therapy," says Vescovi. Noting that hematopoietic
stem cells, the bone marrow cells that give rise to blood, are difficult to
grow and manipulate, the researcher suggests that neural stem cells might
substitute for the treatment of many blood disorders.
"We have no problems expanding endless supplies of neural stem cells,
and we even have human neural stem cells now," comments Snyder. "I'd
be ecstatic if . . . the cells I've isolated with one intent can now address a
magnitude-greater level of diseases."
Neural stem cells may have a future outside the bloodstream as well.
"We're actively investigating whether our [neural] stem cells can give
rise to other solid organs. For instance, can they give rise to muscle or
liver?" asks Snyder.
In addition to searching for the chemical cues that switch neural stem cells
into blood producers, Vescovi plans to study whether hematopoietic stem cells
or other nonneural tissues can give rise to brain cells.