Mar. 9, 2001 SAN FRANCISCO -- Researchers from Duke University Medical Center report taking what they believe is the first important step toward creating functional cartilage from a virtually limitless source -- human fat.
Using a biochemical cocktail of different steroids and growth factors, the researchers demonstrated that they could "retrain" specific cells that would normally form the structure of fat into another type of cell known as a chondrocyte, or cartilage cell. Not only were the researchers able to make cells change from one type into another in the laboratory, they grew the new chondrocytes in a three-dimensional matrix, a crucial advance for success in treating humans with cartilage damage.
Researchers have been able to create cartilage cells from undifferentiated stem cells taken from samples of bone marrow, but harvesting such cells is invasive and painful for the donor and the number of cells gained is small. The Duke team, for the first time, demonstrated that cartilage cells can be created from fat removed during liposuction procedures.
"Using an approach very similar to that used to create cartilage cells from bone marrow samples, we are able to grow a 3-D matrix of cartilage," said Geoffrey Erickson, who prepared the results of the Duke research for presentation Tuesday during the annual meeting of the Orthopedic Research Society. Erickson is a graduate student in biomedical engineering.
"These stem cells can go down different pathways depending on the cues they receive from their environment -- in this case we're giving them the cue to turn into cartilage cells," Erickson said. "This holds out the possibility, some time in the future, of taking fat cells from someone with a cartilage injury and growing new cartilage within a mold to replace the damaged tissue." Cartilage is a type of connective tissue that lines many joints throughout the body. However, since it 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.
"For people who suffer a cartilage-damaging injury, we don't currently have a satisfactory remedy," said Farshid Guilak, director of orthopedic research and senior member of the research team. "There is a real need for a new approach to treating these injuries."
The Duke researchers were surprised at how quickly they were able to prove in concept that they could grow chondrocytes from fat cells. In their series of experiments, the team used the materials collected from liposuction procedures performed on multiple human donors. These materials were then treated with a series of enzymes and centrifuged until cells, known as adipose-derived stromal cells, remained.
These isolated cells were infused into three-dimensional beads made up of a substance known as alginate, a complex carbohydrate that is often used as basis of bioabsorbable dressings, and then treated with the biochemical cocktail.
"After two weeks of growth, the treated cells looked and acted like normal chondrocytes when compared to the untreated cells," Guilak said. "Cells isolated from body fat were producing the proteins and other substances that normal chondrocytes would."
Guilak estimated that it might be three to five years before this approach becomes a clinical reality.
"For patients with cartilage damage, we envision being able to remove a little bit of fat, and then grow customized, three-dimensional pieces of cartilage which would then be surgically implanted in the joint," Guilak said. "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."
At this point, the researchers said they view their approach as initially helping those people who injure their joints as a result of trauma or sports injury. Patients with osteoarthritis, a disease that causes the deterioration of cartilage in joints, would not initially be candidates until the cause of the disease can be determined and addressed.
Collaborating with the Duke team was Dr. Jeff Gimble of Durham-based Artecel Sciences, which holds the patent for the process of isolating these stromal cells from fat. The research was funded by the National Institutes of Health and Artecel Sciences.
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