Bone marrow cells take on new role in the brain
Feb. 6, 2003
STANFORD, Calif. - Researchers in the Baxter Laboratory at Stanford
University Medical Center have published new evidence showing that cells
from the bone marrow might help repair or maintain cells in other tissues.
In a paper in this week's online edition of the Proceedings of the National
Academy of Sciences, the researchers describe finding chromosomes from a
bone marrow transplant in the brain cells of transplant recipients.
When people receive a bone marrow transplant after high-dose
chemotherapy, some of the transplanted cells regenerate the blood-making
cells that were destroyed. In past experiments in mice, Helen Blau, PhD, the
Donald E. and Delia B. Baxter Professor of Pharmacology at the School of
Medicine, found that cells from the transplant could also relocate to
tissues throughout the body rather than being restricted to the bone marrow
and blood.
"Now we know that it can also happen in humans," said James Weimann, PhD,
first author on the paper and a senior research scientist in Blau's lab.
Blau and Weimann looked at brain samples taken from women who underwent
chemotherapy to treat their leukemia and then later received bone marrow
transplants from male donors. These samples were ideal for this experiment
because the donor cells contained a Y sex chromosome whereas cells in the
women contained only X chromosomes. Any Y chromosome that Blau and Weimann
identified must have come from the transplant donor.
To look for the telltale Y chromosome, the researchers used molecules
with a double identity. One part of the molecule could bind to either the X
or Y chromosome, while the other part acted as a fluorescent molecular
beacon. The molecule that bound the X chromosome had a red beacon whereas
the Y-recognizing molecule had a green beacon. When they put these stains on
the preserved samples, the X chromosomes glowed red and any Y chromosomes
glowed green. Weimann then searched the samples under a microscope for green
chromosomes in the brain tissue.
As expected, blood cells within the brain contained Y chromosomes because
they were made by bone marrow cells from the transplant. The researchers
also found five nerve cells called Purkinje cells - involved in controlling
balance and movement - that contained Y chromosomes in addition to their
original X chromosomes. These out-of-place chromosomes could only have come
from male cells in the bone marrow transplant.
Blau suspects the Purkinje cells may have gotten their Y chromosome from
a group of traveling bone marrow cells. "I think these cells may act as a
repair squad," Blau said. The cells travel the bloodstream, respond to
stress and repair damaged tissues such as brain, muscle and possibly others
throughout the body. She added that in some cases the bone marrow cells
might fuse with damaged cells while in other instances they transform to
replace the cells.
She said the next steps are to learn which cells in the bone marrow act
as the repair squad, how these cells are lured to tissues and how they
repair damage once they get there. "If we can learn what the signals are, we
may be able to direct the repair cells to where they are needed," Blau said.
"Wouldn't it be terrific if we could enlist the body to treat its own
disease?"
Blau added that adult bone marrow cells may be particularly useful for
treating some diseases or some tissues but not others. "We need to study all
types of stem cells," she said.
Other Stanford researchers who contributed to this work include Carol
Charlton, PhD, a research associate, and graduate student Timothy Brazelton,
PhD.
Stanford University Medical Center
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