In the first hours and days following a stroke, stem cells
leave the bone marrow to help the injured brain repair damaged
neurons and make new neurons and blood vessels, according
to researchers at the Medical College of Georgia.
The research, reported in the May issue of Stroke, used
a mouse model in which the animal's marrow was replaced with
that of a transgenic mouse with cells that make a jellyfish
protein that fluoresces green so they could trace the cells
and the natural repair process that apparently occurs after
The researchers are now looking for the right factors to
enhance the normal repair mechanism, improve stroke recovery
and, since the patient's own cells would be used, avoid issues
such as the compatibility of donated stem cells and the ethical
controversy surrounding embryonic stem cells.
They also want to identify which bone marrow stem cell types
are targeted for this repair and how they are called to the
site of injury, suspecting that inflammation may be part of
this 'homing" process.
"We tried to determine whether cells that reside in
your bone marrow and circulate throughout the blood could
turn into any of the major brain cells types," said Dr.
David Hess, neurologist, stroke specialist, chairman of the
MCG Department of Neurology and lead author on the study.
They found in the animal model, evidence that bone marrow
cells naturally migrate to injured regions of the brain after
stroke to help repair damaged tissue; they also become endothelial
cells that form new blood vessels and what appear to be new
"Such repairs occurred naturally in response to stroke
and the bone marrow is involved in those repair mechanisms,"
said Dr. William D. Hill, neuroscientist in the MCG Department
of Cellular Biology and Anatomy and second author on the research
"We think that when you have a stroke, you have this
central core area that is highly affected. Then you have this
area like a shell surrounding the core, called the penumbra,
like a shadow that has a gradient of damage as you move from
the core of the stroke to the unaffected tissue. This is the
area that is going to be the most sensitive to being repaired.
So maybe if we can enhance that repair, we could preserve
a region that would normally die but is an area we can target
Enhancement could come through the use of growth factors
that affect subsets of bone marrow cells; possibly some already
on the market, for example to help leukemia patients rebuild
bone marrow after chemotherapy, might be useful.
"If this works out, you will be able to give individuals
shots following stroke to boost their bone marrow to proliferate
these stem cells to do specific tasks, target specific groups
of these stem cells important to blood vessel repair and the
genesis of new neurons," Dr. Hill said. The work has
implications for all sorts of brain injuries early and late
in life such as cerebral palsy, Parkinson's and Alzheimer's
This repair process mimics embryological development when
stem cells from the bone marrow help form blood vessels in
the brain. "There are some data that older people don't
have as many circulating stem cells as younger, healthier
people do," Dr. Hess said, so enhancing the cell number
involved in repair should enhance the natural process.
Enhancing the natural process could avoid more aggressive
measures such as transplanting cell-laden bone marrow. "Why
would we transplant bone marrow cells into people when their
bone marrow already has these cells?" Dr. Hess said.
"It makes much more sense to actually maximize what they
already put out. Also, rather than taking bone marrow out
and injecting it into the brain, why not make use, again,
of this natural process that summons the cells to the location
of the brain injury?"
Finding what summons the cells to the injury site is key,
and the researchers are looking at specific molecules up-regulated
in inflammation that they suspect are also involved in homing.
"Certain factors released and expressed on the surface
of damaged endothelial cells may act as flags to wave down
passing white blood cells or stem cells to attach there,"
Dr. Hill said.
Also key is identifying which specific stem cells are summoned
and are needed to make new blood vessels, support cells and
neurons. This may permit selective recruitment and proliferation
of just the cells needed for repair, Dr. Hill said.
There are two known broad classes of these cells, hematopoetic
and mesenchymal, but there may be many unknown cell types,
including a separate group involved in making endothelial
cells, Dr. Hess said.
Just last week, through a collaborative study with the Medical
University of South Carolina, they received the first mouse
that, through a process called clonal analysis, will enable
them to tag a single cell, then watch for its descendents'
roles in the normal repair process.
They also are collaborating with fellow MCG researcher Nevin
Lambert to do a functional analysis of the new neurons produced
by the stem cells to ensure that they not only look like but
function as neurons.