Bone marrow generates new neurons in human brain
Jan. 23, 2003
A new study strongly suggests that some cells from bone marrow can
enter the human brain and generate new neurons and other types of brain
cells. If researchers can find a way to control these cells and direct them
to damaged areas of the brain, this finding may lead to new treatments for
stroke, Parkinson's disease, and other neurological disorders. \
"This study shows that some kind of cell in bone marrow, most likely a
stem cell, has the capacity to enter the brain and form neurons," says Eva
Mezey, M.D., Ph.D., from the National Institute of Neurological Disorders
and Stroke (NINDS), who led the study. Earlier work by Dr. Mezey and others
has shown that bone marrow cells can enter the mouse brain and produce new
neurons. However, the new study is the first to show that this phenomenon
can occur in the human brain. The study was supported in part by the NINDS
and appears in the January 20, 2003, online early edition of the
"Proceedings of the National Academy of Sciences" (1). The NINDS is a
component of the National Institutes of Health, which is part of the U.S.
Department of Health and Human Services.
In the study, Dr. Mezey and colleagues examined brain tissue taken at
autopsy from four female patients -- two adults and two children -- who had
received bone marrow transplants from male donors. The bone marrow
transplants had been performed to treat leukemia and other non- neurological
diseases, and the patients survived from 1 to 9 months after their
transplants. The investigators searched the autopsied brain tissue for male
cells, which contain a Y chromosome. The Y chromosomes in these cells served
as a useful way of distinguishing donor-derived cells from those of the
female transplant recipients. The researchers found cells with Y chromosomes
in brain tissue from all four of the patients.
Most of the bone marrow-derived cells in the brain tissue were glia
(support cells) and other non-neuronal cells. However, a small number of
neurons from each brain also contained Y chromosomes, showing that those
cells had developed from the transplanted male bone marrow. Most of these
neurons were found in the cerebral cortex -- the outer layer of the brain,
which is responsible for conscious thought -- and in the hippocampus, a
region that helps with memory and other functions.
The Y chromosome-positive cells within each patient's brain appeared in
clusters, rather than being randomly dispersed throughout the brain tissue.
The clusters sometimes contained both neuronal and non-neuronal cells. This
suggests that a single bone marrow-derived stem cell may migrate into an
"area of need" within the brain and then change, or differentiate, into
several other kinds of cells, Dr. Mezey says. The clusters also might result
from a large number of marrow cells that are "called" to specific parts of
the brain. Previous studies have suggested that stem cells can respond to
signals from within the brain that guide them to damaged regions.
The brain sections with the largest number of marrow- derived neurons
came from the youngest of the four patients, who had her transplant at 9
months of age. That patient also survived for 9 months after the transplant
-- much longer than the other patients in this study. The researchers do not
know if the number of marrow-derived neurons in this patient was due to her
young age or to the length of time she survived after receiving the
transplant. The brains of young people usually undergo more changes than
those of older people, and this might have encouraged the development of new
neurons, Dr. Mezey notes. However, it is also possible that new cells enter
the brain at a steady rate over time, regardless of a person's age.
It is possible that irradiation or other treatments that the four
patients received might have increased the ability of marrow cells to enter
the brain. However, other studies have suggested that bone marrow cells
circulating in the blood enter the brain even in healthy subjects who have
never received a bone marrow transplant, and there is no reason to think
that a transplant is necessary for stem cells to enter the nervous system,
Dr. Mezey says.
The numbers of marrow-derived neurons identified in the human brain
tissue were very low -- much lower than the numbers identified in a previous
mouse study, says Dr. Mezey. However, the numbers might be greater in
patients who survive for longer periods after transplant, she suggests.
Bone marrow contains at least two kinds of stem cells: hematopoietic stem
cells, which usually differentiate into blood cells, and mesenchymal stem
cells, which can differentiate into many kinds of cells in the body. The
researchers do not yet know which type of cell differentiates into the
neurons and other marrow-derived cells they identified in the brain.
Recent studies have shown that instead of developing into new cell types,
adult stem cells sometimes fuse with mature cells from existing tissues that
have already undergone differentiation. The resulting cells carry four sex
chromosomes (X and Y chromosomes) instead of the usual two. While Dr. Mezey
and her colleagues cannot exclude the possibility that fusion accounts for
their results, they looked at several hundred donor-derived cells from one
of the patients and did not see doubled sex chromosomes in any of the cells
they examined.
Previous studies have found some cells with Y chromosomes in adult women
who had not received any transplants. Researchers believe these Y cells may
have come from a past pregnancy with a male fetus. However, two of the
subjects in this study were children, and the male cells in those
individuals could not have come from a pregnancy, says Dr. Mezey.
Scientists must now determine what growth factors or other signals prompt
the bone marrow cells to enter the brain and develop into neurons. This may
lead to new ways of treating Parkinson's disease or other disorders where
neurons lost to disease are not normally replaced. Researchers might also be
able to discover factors that can increase the number of cells entering the
brain or prompt the cells to find useful targets.
"These studies are very much the beginning, but scientists should start
to look down this road and find out if and how we can go further," says Dr.
Mezey. She cautions that it is too early to know if this finding will lead
to useful treatments for neurological disorders. She and her colleagues are
now planning to study brain tissue from people who survived for longer
periods after receiving a bone marrow transplant in order to see if the
number of marrow-derived neurons increases with time. They also plan to
study mice to determine which cells in the bone marrow develop into neurons.
The NINDS is the nation's primary supporter of biomedical research on the
brain and nervous system.
National Institutes of Health
|
