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Reprogrammable Cells From Fat Are True Adult Stem Cells

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Duke Health News 919-660-1306

SAN FRANCISCO -- After successfully turning cells taken from
human fat into different cell types, Duke University Medical
Center researchers have now demonstrated that these specific
cells are truly adult stem cells with multiple potential,
instead of being a mixture of different types of cells, each
with a more limited destiny.

During the past three years, the Duke researchers exposed
cells taken from human liposuction procedures to different
cocktails of nutrients and vitamins, and "reprogrammed" them to
grown into bone, cartilage, fat and nerve cells. At the time,
they termed these cells adipose-derived stromal cells.

However, as a result of the latest set of experiments, the
researchers are now confident that the majority of these cells
are indeed truly adult stem cells that have the potential to be
reprogrammed into traveling down multiple developmental paths.
This is important, they said, because these cells could be a
single, readily available source for creating new cells and
tissues to treat disease.

The results of the Duke study were presented March 8, 2004,
at the 50th annual scientific meeting of the Orthopedic
Research Society by Kristen Lott, a fourth-year medical student
working in the laboratory of Farshid Guilak, Ph.D., director of
orthopedic research and senior member of the Duke team.

"Our findings indicate that 62 percent of the human fat
cells could be reprogrammed into turning into at least two
other different cell types," Lott said. "This percentage of
cells is quite high, meaning that they have a great deal of
flexibility and that their ultimate destiny may not be so
pre-determined.

"These results suggest that these cells are truly stem cells
that could provide a source of undifferentiated cells for
multiples uses," Lott continued. "We're still a long way from
using these cells as therapies in humans, but we're excited
about the progress we've made so far."

Added Guilak, who is also on the faculty of Duke's Pratt
School of Engineering, "We don't know exactly why body fat
contains stem cells that can form bone or cartilage, but it
does help dispel the dogma that adult stem cells can only be
found in the bone marrow."

For their study, the Duke team took liposuction samples from
three adult donors and then grew clones of these cells for up
to 25 doublings. The cells were then exposed in culture to one
of the four recipes -- mixtures of vitamins, growth factors and
steroids -- for reprogramming cells into either fat, bone,
cartilage or nerve cells.

While 62 percent of the cells were able to be "guided" down
at least two different paths, only 10 percent failed to
differentiate into any of the four cell types, Lott said.

"Additionally, the results of this study offer criteria for
defining stem cell multipotency that should help researchers in
further investigations," Guilak said. "More of the clones
developed into bone, cartilage and nerve cells than they did
into fat cells, which is another interesting finding."

Guilak believes that as a result of the successive
culturing, the stem cells may have lost their ability to turn
into fat cells.

"Our experiments took the cells through many doublings,"
Lott said. "Since these cells would potentially be in people
for longer, we still need to better understand what happens to
these cells over time."

The researchers anticipate that the first patients to
benefit from this research are those who have suffered some
sort of cartilage damage due to injury or trauma. Farther down
the line, they foresee a time when entire joints ravaged by
osteoarthritis can be relined with bioengineered cartilage.

"We don't currently have a satisfactory remedy for people
who suffer a cartilage-damaging injury," Guilak said. "There is
a real need for a new approach to treating these injuries. We
envision being able to remove a little bit of fat, and then
grow customized, three-dimensional pieces of cartilage that
would then be surgically implanted in the joint. One of the
beauties of this system is that since the cells are from the
same patients, there are no worries of adverse immune responses
or disease transmission."

The study was funded by the National Institutes of Health
and the North Carolina Biotechnology Center.

Other members of the research team were Hani Awad, Ph.D.,
from Duke and Jeffrey Gimble, M.D., from the Pennington
Biomedical Research Center at Louisiana State University.

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