Reprogrammable Cells From Fat Are True Adult Stem Cells

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.