Feb. 11, 2002 DALLAS -- Duke University Medical Center researchers have "reprogrammed" adult stem cells taken from a small deposit of fat behind the kneecap into functioning cartilage, bone or fat cells that could potentially be grown into replacement tissues.
The research team, which reported last year that they were able to turn fat cells taken from liposuction procedures into functional cartilage cells, provides further evidence that stem cells taken from different adult sources have the potential to be transformed into multiple specialized cell types.
"In scientific terms, we have found a new source of adult stem cells that can be changed into different cells and tissues," said M. Quinn Wickham, who presented the results of the Duke research today (Feb. 10) at the annual meeting of the Orthopedic Research Society. Wickham is a fourth-year medical student working in the laboratory of Farshid Guilak, director of orthopedic research at Duke and senior member of the research team.
"On the clinical side, for example, it would be relatively easy for a knee surgeon to obtain some of these fat cells using a minimally invasive approach," Wickham continued. "We could then grow cartilage custom-made for the individual to repair an injury in the knee with the patient's own tissue."
The fat pad is a dense structure behind the patella, or kneecap, that is unlike typical fat tissue found throughout the body, the researchers said. While its function is not well understood, researchers do know that it is metabolized much more slowly than subcutaneous fat.
"This is another demonstration that adult stem cells are not necessarily locked into their current fate, and furthermore, we can reprogram them into becoming other cell types," Guilak said. "It is unlikely that one source of stem cells can be used to treat the wide variety of medical problems and diseases, but different clinical problems could be addressed by using adult cells taken from different spots throughout the body, without the same ethical concerns associated with embryonic stem cells."
In the current study, the researchers took the fat pads from patients whose knee joints were removed during total joint replacement surgery. The researchers focused on specific cells within the samples known as adipose-derived stromal cells, which under normal situations would receive environmental cues to transform themselves into fat pad cells. After the samples were treated with a series of enzymes and centrifuged, the separated stromal cells were treated with a biochemical cocktail of different steroids and growth factors.
"By treating these stromal cells with different agents, we were able to induce them to commit to multiple lineages," Wickham said. "These findings suggest that the fat pad, given its location and accessibility, may prove to be an excellent source of progenitor cells for tissue engineering or other cell-based therapies."
In addition to controlling their biochemical environment, the researchers were able to grow different cell types from the adult stem cells by controlling their shape in a three-dimensional matrix, a crucial advance for using resulting tissues as human therapies. To grow cartilage, groups of cells were infused into a matrix made of a substance known as alginate, a complex carbohydrate that is often used as the basis of bioabsorbable dressings.
The therapeutic potential for tissues grown from these adult stem cells is large and varied, Wickham said.
"For example, fat tissue could be custom grown for use in reconstructive or cosmetic cases performed by plastic surgeons," Wickham said. "The bone tissue could be used to repair bone defects caused by disease or trauma." Since cartilage is a tissue type that is poorly supplied by blood vessels, nerves and the lymphatic system, it has a very limited capacity for repair when damaged. The researchers believe that this would be one of the earliest therapeutic uses of such tissue engineering techniques.
"For patients with tissue damage, we envision being able to remove a small piece of fat, and then growing customized, three-dimensional pieces of tissue which would then be surgically implanted where needed," Guilak continued. "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. However, we would still like to test whether cells from a person's fat tissue could be used to treat another patient without being rejected."
Guilak estimated that it might be more than five years before this approach becomes a clinical reality. However, based on the results of numerous prior animal studies, and the results of the current experiments, the researchers are confident that this strategy has potential. Collaborating with the Duke team was Dr. Jeff Gimble of Durham, N.C.-based Artecel Sciences, who holds the patent for the process of isolating these cells from fat. Guilak is a consultant for Artecel Sciences.
Other members of the team, from Duke, were Geoffrey Erickson and Dr. T. Parker Vail.
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