Stem Cell 'Homing' Fixes Joints in Rabbit Experiments

Researchers are reporting they have successfully persuaded damaged joints to regrow cartilage and bone using a novel "cell homing" approach.

The experiments, conducted in rabbits, are a proof of concept of a method that may one day replace artificial joint transplants in humans, according to Jeremy Mao of Columbia University and colleagues.

The method uses a carefully constructed "bioscaffold," impregnated with a natural substance called a growth factor. the growth factor in the scaffold causes precursor cells to migrate to the site and become cartilage and bone cells, Mao and colleagues wrote online in The Lancet.

In contrast with previous attempts to regrow tissue in joints, the researchers reported that they did not transplant any cells.

Animals treated with the method fully recovered weight-bearing and locomotion within a month, and the regenerated tissue was similar to naturally occurring cartilage and bone, the researchers said.

The findings are "a substantial step" toward being able to grow individually customized replacement joints for patients who now would be treated with total joint replacement, according to Dr. Patrick Warnke of Bond University in Gold Coast, Australia.

Warnke led researchers who in 2004 reported growing a mandible bone in the muscle tissue of a man who had a defect in the mouth after cancer surgery. The bone was later transplanted successfully to the man's jaw.

The new research, Warnke wrote in an accompanying editorial, "offers new insights into in-vivo tissue engineering."

In the experiments, the researchers first used laser scanning and computer-aided design to construct an anatomically correct model of the surface of a joint found in the front legs of rabbits out of a mixture of polyester and bone.

In 20 animals, the entire joint surface of this leg joint was surgically removed and replaced with these bioscaffolds. Half of these contained the growth factor, while half did not. Three other animals underwent the surgery and had no implant.

The researchers assessed the ability of the rabbits to move around and put weight on the new joint over the eight weeks immediately following the surgery, and at four months they retrieved regenerated cartilage samples from the animals and assessed them for a range of properties, including thickness, density, and the number of cartilage cells.

They found:

All animals that got the growth factor fully resumed weight-bearing and locomotion within four weeks of surgery, and by eight weeks they moved almost as well as animals that had not been operated on.

Their recovery was more consistent than animals that got the implant without the growth factor, while the rabbits that just had the surgery limped at all times. Four months after surgery, the growth factor-infused implants were completely covered with hyaline cartilage, while the animals that got just the implants had only isolated patches of cartilage. There was no cartilage formation in the three animals without an implant.

The growth factor recruited roughly 130 percent more cells in the regenerated cartilage than did spontaneous cell migration without it, the researchers reported.

The implication is that the growth factor acts as a "chemotactic cue for cell homing," they argued.

The method has potential for treating humans, Warnke said, but there are some possible drawbacks. For one thing, he wrote, many potential patients are elderly and have comorbidities such as diabetes that might impair their regenerative capacity.

And the physiotherapy that would be needed to ensure that the regenerated tissue was smooth and well-articulated might be too onerous for some patients and a standard replacement joint is likely to be faster and less demanding.

On the other hand, he said, the method might be valuable in younger patients needing a joint replacement.