|
Ed. Note: The following is a press release issued by Duke
University.
6/1/2004
DURHAM, N.C. -- Two years after transforming human fat cells into what
appeared to be nerve cells, a group led by Duke University Medical Center
researchers has gone one step further by demonstrating that these new cells
also appear to act like nerve cells.
The team said that the results of its latest experiments
provide the most compelling scientific evidence to date
that researchers will in the future be able to take
cells from a practically limitless source -- fat -- and
retrain them to differentiate along new developmental
paths. These cells, they said, could then be used to
possibly treat a number of human ailments of the central
and peripheral nervous systems.
The results of the team's latest experiments were
published June 1, 2004, in the journal Experimental
Neurology.
Using a cocktail of growth factors and induction agents,
the researchers transformed cells isolated from mouse
fat, also known as adipose tissue, into two important
nerve cell types: neurons and glial cells. Neurons carry
electrical signals from cell to cell, while glial cells
surround neurons like a sheath.
"We have demonstrated that within fat tissue there is a
population of stromal cells that can differentiate into
different types of cells with many of the
characteristics of neuronal and glial cells," said
Duke's Kristine Safford, first author of the paper.
"These findings support more research into developing
adipose tissue as a viable source for cellular-based
therapies."
Over the past several years, Duke scientists have
demonstrated the ability to reprogram these
adipose-derived adult stromal cells into fat, cartilage
and bone cells. All of these cells arise from
mesenchymal, or connective tissue, parentage. However,
the latest experiments have demonstrated that
researchers can transform these cells from fat into a
totally different lineage.
Earlier this year, Duke researchers demonstrated that
these adipose-derived cells are truly adult stem cells.
As a source of cells for treatment, adipose tissue is
not only limitless, it does not carry the potentially
charged ethical or political concerns as other stem cell
sources, the researchers said.
"This is a big step to take undifferentiated cells that
haven't committed to a particular future and redirect
them to develop down a different path," said Duke
surgeon Henry Rice, M.D., senior member of the research
team. "Results such as these challenge the traditional
dogma that once cells become a certain type of tissue
they are locked into that destiny. While it appears that
we have awakened a new pathway of development, the exact
trigger for this change is still not known."
For their latest experiments, the researchers
demonstrated that the newly transformed adipose cells
expressed many similar cellular proteins as normal nerve
and glial cells. Furthermore, they showed that the
function of these cells is similar to nerves.
They exposed these newly formed cells to N-methyl-D-aspartate
(NMDA), an agent which blocks the activity of the
neurotransmitter glutamate and is toxic to nerve cells.
In response to NMDA, the newly induced cells died, a
response similar to normal nerve cells under the same
conditions. Physiologic insults -- such as stroke -- can
stimulate NMDA receptors on nerve cells, which can cause
nerve cell damage or death by over-stimulating them.
"We found that these induced adipose cells demonstrated
an excitotoxic response to NMDA that corresponded with a
loss of cell viability, which suggests that these
induced cells had formed functional NMDA receptors
similar to those found on nerve cells," Rice explained.
"Recent studies have demonstrated that NMDA receptor
activation by glutamate may induce early gene
transcription in developing neurons as well as determine
the rate of neuronal proliferation in the brain. Our
findings suggest that these induced cells exhibit
characteristics similar to developing neuronal tissue."
Now that the researchers are confident that these newly
induced cells appear to have similar functions as nerve
cells, the next step will be to see how they respond
when they are implanted a living animal model.
"While this is an important step forward, we still face
many challenges to making use of these cells to treat
human problems," said longtime collaborator Jeffrey
Gimble, M.D., Pennington Biomedical Research Center at
Louisiana State University System. "It seems probable
that the potential first uses of such therapy would be
in an acute setting, where you would have a window of
opportunity right after a stroke, or spinal cord or
peripheral nerve injury."
Until recently, it was believed that organisms were born
with the full complement of neuronal cells, and that new
neurons could not be formed. According to the
researchers, the findings of their studies, as well as
the experiments performed by others on bone marrow stem
cells, opens up new possibilities for the treatment of
nervous system disorders or injuries.
"We are trying to think about human disease in a new
way," Gimble said. "Everyone is used to the concept of
surgical, medical or pharmacological approaches to the
treatment of disease -- we're looking at one of the next
steps in biotechnology, which is using cellular
therapies."
The current research was supported by the Owen H.
Wangenstein, M.D., Faculty Research Fellowship of the
American College of Surgeons. Other members of the Duke
team included Shawn Safford, M.D., and Ashok Shetty,
Ph.D.
media contact :
Richard Merritt , (919) 684-4148
merri006@mc.duke.edu
Return To Table Of
Contents |