August 16, 2010

Coaxing the Body’s Cells to Repair Damaged Joints

Photos of a porous scaffold with and without a thin layer of new cartilage Researchers created porous scaffolds (left) shaped like the tip of a rabbit’s leg bone. When embedded with growth-enhancing proteins and implanted in an injured joint, the scaffold supported the growth of new cartilage tissue (right). Lee et al., Lancet

Scientists have developed a technique that leads to the successful regrowth of damaged leg joints in rabbits. The accomplishment shows that it’s possible to lure the body's own cells to injured regions and generate new tissues, such as cartilage and bone. The finding could point the way toward joint renewal in humans.

Joint disorders are becoming increasingly common as the population ages. Osteoarthritis—a condition marked by the structural breakdown of cartilage and bone—is a leading cause of chronic disability worldwide. Severe cases may require joint replacement surgery, often with artificial metal joints that last for about 10 or 15 years. To find longer-lasting alternatives, scientists have explored using stem cells to grow replacement tissues outside the body before transplantation into joints. Success so far has been limited.

Taking a different approach, Dr. Jeremy J. Mao of Columbia University and his colleagues fabricated biodegradable, porous scaffolds in the shape of a leg bone's rounded tip. They tested to see if the bioscaffold, when implanted into a rabbit’s leg joint, could naturally attract the body’s own stem cells and encourage the growth of new tissues. Their research was supported by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and New York State Stem Cell Science.

The scientists treated the damaged leg joints of 20 rabbits by implanting bioscaffolds infused with a collagen gel. In 10 of the rabbits, the gel was also loaded with a protein called transforming growth factor β3 (TGFβ3), which is known to be involved in cartilage development. Three rabbits with damaged leg joints received no implants.

As described in the July 29, 2010, early online edition of the Lancet, the researchers found that by 3 to 4 weeks after surgery, rabbits with TGFβ3-infused bioscaffolds were able to move around almost as well normal rabbits. In contrast, the untreated rabbits continued to limp at all times.

By 4 months after surgery, both bone and cartilage had regenerated in the treated joints. The TGFβ3-infused bioscaffolds showed the greatest improvement. These implants had grown a whole layer of cartilage tissue and had recruited 130% more cells to the joint area than did the bioscaffolds without the TGFβ3. The compressive and shear properties of the TGFβ3-infused cartilage layers were similar to those of normal cartilage and were significantly better than the cartilage on the TGFβ3-free scaffolds.

"This is the first time an entire cartilage joint was regenerated," says Mao. "This is a rare example of regenerating complex tissues by recruiting the body's internal stem cells, rather than the typical approach of taking stem cells out of the body. By successfully regenerating cartilage in this way, we hope that this approach would work with other tissues without cell transplantation."

Mao and his colleagues note that the new method might help to sidestep some of the problems inherent in cell transplantation, including immune system rejection and transmission of disease-causing microbes. Significant research is needed, however, before the technique could be tested for repairing human joints.

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