Scientists convert fat cells to cartilage

Duke researchers have engineered a method of converting human fat-a virtually limitless source-into functional cartilage, which may be used in the future to replace damaged tissue.

"There's been a growing interest in tissue engineering because it involves regenerating necessary tissue [using cells from a host] and re-implanting it back into the host," said senior research team member Dr. Farshid Guilak, Duke associate professor of medicine. "Since fat, bone and cartilage all come from the same tissue, they are interrelated, and we hypothesized that the cells making fat could probably be retrained to make other cells [under different conditions]."

Using a biochemical cocktail of growth factors and vitamins, the researchers were able to turn specific, undifferentiated cells that normally form adipose cells, or fat, into cartilage. The researchers were also able to grow these cartilage cells for the first time in a three-dimensional matrix, a strong indication that they may be successfully used in replacing human cartilage.

Cartilage is connective tissue that lines many joints in humans but cannot regenerate or repair itself after damage because it has poor blood supply and nerve infrastructure.

The Duke researchers, including Guilak and biomedical engineering graduate student Geoffrey Erickson, worked in conjunction with Artecel Sciences, a Durham-based company that holds the patent on growing purified, undifferentiated cells from fat tissue. These stromal cells are multipotent and can develop into various types of specialized cells. While it is too early to define the exact mechanism underlying the formation of cartilage from these cells, researchers believe they have some clues. "In general, we have created a mini-environment for the cells that gives them cartilage-forming signals rather than fat-forming signals," said Dr. Jeff Gimble, vice president of Tissue Engineering at Artecel Sciences. "In addition, the cells need to be kept in relative isolation from each other so they need to be suspended in an artificial matrix. This combination of microenvironmental cues is probably responsible for our findings."

The researchers have also started preliminary studies where stromal cell-induced cartilage has been implanted into the backs of mice. Although preliminary, the results seem to show that animals will support the chemically synthesized cartilage. Among other plans, the researchers are interested in optimizing the growth medium and conditions of the lab procedure and ensuring that the stromal cell-induced cartilage has the same properties, durability and biomechanics of real cartilage. If these goals are met, researchers plan to start clinical trials as soon as possible.

"This finding is a step in the right direction, especially when current treatments for cartilage damage possess various limitations," Erickson said. "Younger athletes with knee injuries, for instance, currently have limited options and may have to wait years before their doctor will order a knee replacement."

Researchers are optimistic about the possibilities that this finding provides. "If [the clinical trials are positive], we will have found an unlimited source for tissue repair," Guilak said. "If finding cells is no longer the limiting factor, then we will be able to make permanent living tissue replacements in the long-term."