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From: "Laura Jane Cohen" <[log in to unmask]>

U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News Release

National Institute of Neurological Disorders and Stroke

EMBARGOED FOR RELEASE
Monday, January 20, 2003
5:00 p.m. ET

Contact:
Natalie Frazin
(301) 496-5751


BONE MARROW GENERATES NEW NEURONS IN HUMAN BRAINS

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.
----------------------------------------------
1) Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD,
Crain B. "Transplanted bone marrow generates new neurons
in human brains." 'Proceedings of the National Academy
of Sciences', Online Early Edition, January 20, 2003.

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