Turning Blood into Brain: New Studies
Suggest Bone Marrow Stem Cells Can Develop into Neurons in Living Animals
For release: Thursday, November 30, 2000
For years, researchers studying stem cells have been intrigued by the
possibility that these cells might be used to treat brain diseases. Recent
studies have suggested that neural stem cells transplanted into the brain can
migrate throughout the brain and develop into other types of cells. Now, two new
studies show that bone marrow cells transplanted into mice can migrate into the
brain and develop into cells that appear to be neurons. The studies suggest that
bone marrow may be a readily available source of neural cells with potential for
treating such neurological disorders as Parkinson's disease and traumatic brain
injury.
While previous research has shown that bone marrow cells can develop into
neuron-like cells in culture, the new studies are the first to show that this
process can also happen in living animals. The two studies reached the same
conclusion despite many differences in how the studies were performed. The
results are reported in the December 1, 2000, issue of Science.
"These are extraordinarily important studies, carefully done, with clear
implications for brain disorders and for basic developmental biology," says
Gerald D. Fischbach, M.D., director of the National Institute of Neurological
Disorders and Stroke (NINDS).
In the first study,1 NINDS investigator Eva Mezey, M.D., Ph.D., and colleagues
injected bone marrow cells from normal male mice into newborn female mice that
had no white blood cells of their own. Using marrow from male mice allowed the
researchers to use the Y chromosomes in the transplanted cells as a marker to
distinguish them from native cells. At different time intervals, the researchers
examined cells from the brains of seven mice that had received the transplants
and compared them to littermates that had not received the transplants. By 4
months after the transplants, they found a significant number of neuronal cells
in several brain regions, including the cortex, the hypothalamus, and the
striatum, that were descendants of the transplanted cells. This suggests that
stem cells from elsewhere in the body can enter the brain and differentiate into
neuronal cells, says Dr. Mezey.
In the second study,2 Helen Blau, Ph.D., and colleagues from Stanford University
injected bone marrow from adult mice that express a marker called green
fluorescent protein (GFP) into adult mice that had been irradiated to eliminate
their bone marrow. They found that bone marrow-derived cells migrated into
several regions of the brain, including the olfactory bulb, the cortex, the
hippocampus, and the cerebellum. Some of the marrow-derived neuronal cells also
grew long fibers and produced a protein that indicates cell activity.
These results suggest that the marrow-derived neurons not only entered the brain
but also responded to their environment and began to function like the native
ones.
These studies suggest that bone marrow, which is an easily available source of
cells, could be used as a source of neurons to replace those damaged or lost in
neurological disorders, the researchers say. It might also be possible to
genetically engineer the cells in ways that would help them survive or work in
beneficial ways. The fact that even bone marrow from adult mice generated
neuronal cells shows an unexpected amount of flexibility in older cells and
suggests that patients with brain disorders could be treated with their own
cells, says Dr. Blau. Bone marrow cells taken from a patient's own body would
not be rejected by the body's immune system.
While the results are very promising, researchers need to answer many remaining
questions before marrow-derived neural cell therapies can be tested in humans. A
key question is what growth factors and other
signals prompt the bone marrow cells to develop into specific types of neurons.
If researchers can describe how the normal process of cell differentiation
works, they may be able to reproduce it in patients with disorders such as brain
injury or Parkinson's disease where neurons are not normally replaced.
Researchers might also be able to discover factors that help cells enter the
brain or connect with other cells. "We need much more data, but I think
it's a pretty encouraging start," says Dr. Mezey.
Since the studies used whole bone marrow, it is important to determine which
population of bone marrow cells develop into neurons, the researchers say. Other
questions for future studies include whether marrow-derived neurons function
like normal neurons and if they can make appropriate connections with other
cells. The findings in Science should speed the pace of research to answer these
and other important questions, the researchers say. However, they believe it
will be several more years before the results reported in these studies
will lead to effective therapies.
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is
the nation's leading supporter of research on the brain and nervous system. The
NINDS is now celebrating its 50th anniversary.
Image description: Photograph of a neuronal cell derived from bone marrow. The
green spot indicates the Y chromosome which distinguishes this cell from innate
cells. Science/Dr. Eva Mezey, NINDS.
Reporters: for more information contact Natalie Frazin or Margo Warren, NINDS
Office of Communications and Public Liaison, at 301-496-5751.
Reviewed November 30, 2000