"The treatment is safe and feasible," said study co-author, Dr. Ivan Martin.
Between 2004 and 2011, nearly two million Americans
underwent a knee surgery due to cartilage problems. As the population ages, these surgeries will become increasingly common, experts say, however the existing techniques aren't optimal. This study indicates a promising new option could be within sight.
"Moreover, results indicate that the tissue being formed at the patients' repair site improves in composition over time, getting more and more similar to healthy cartilage," said Martin, a professor of surgery and biomedicine at University Hospital Basel in Switzerland. "Patients' satisfaction was also, on average, improving over time."
Joint conditions in the knee often begin with damage to articular cartilage -- the tissue at the end of a bone that cushions the joint. This cartilage is necessary for pain-free movement. Unfortunately, cartilage lacks its own blood supply, so it has very little ability to repair itself once damaged.
Since 2001, Martin and his team have been investigating a new surgical approach to repairing knees. It uses engineered cartilage tissue grown from patients' own cells, taken from the nasal septum.
The rationale behind this is based on the fact that nasal cells "have a larger and more reproducible capacity to form new cartilage," said Martin. In fact, he and his team demonstrated this in past studies.
"We further established that the cartilage tissue generated by nasal chondrocytes [one type of cell] can respond to physical forces (mechanical loads) similar to articular cartilage and has the 'plasticity' to adapt to a joint environment," added Martin. In one of their pre-tests for the current study, he implanted engineered tissue into goat joints and found it "efficiently integrated with surrounding articular cartilage."
For the new study, Martin and his colleagues took the all-important step of testing their ideas in humans. They began by enlisting the help of 10 patients, who range in age from 18 to 55, all with cartilage lesions of the knee.
For each patient, the team began by extracting a small biopsy specimen (6 millimeters in diameter) from the nasal septum under local anesthetic using a minimally invasive procedure. Next, the researchers multiplied the harvested cells by exposing them to growth factors for two weeks.
After seeding the cells onto collagen membranes, the team cultured them for an additional two weeks. The result: a 30 by 40 millimeter cartilage graft. Finally, the surgeons sculpted the engineered graft into the right shape and implanted it as a replacement for damaged cartilage removed from a patient's knee.
The work is similar in concept to using stem cells, according to Dr. David Jevsevar, chair of the American Academy of Orthopedic Surgeon
's Council on Research and Quality. He noted that unlike stem cells, nasal septum cells "are cartilage cells. So they are taking cartilage cells of one type and introducing them into the knee to become an articular cartilage cell."
Time and cell cultures
Over two years, MRI scans revealed new tissue, similar in composition to the original cartilage, had developed in the patients' knees. Nine recipients reported substantial improvements in their knee and less pain than before surgery. (The 10th patient had to be excluded after sustaining several independent sports injuries.)
None of the patients reported side effects related to the experimental surgery. Since this trial did not include a comparison group of patients undergoing other treatments for the same condition, more studies will be needed.
Martin and his co-authors emphasize that their experimental procedure still requires rigorous testing in large clinical trials with longer follow-up periods. Experts in the field agree.
"We obviously need a much bigger study and some additional scientific rigor applied to it," said Jevsevar. Others say time is the main issue.
Long-term results "will be needed to establish whether this technology has the potential to be approved by the European Medicines Agency and the US Food and Drug Administration," wrote Dr. Nicole Rotter of Germany's Ulm University Medical Center and Dr. Rolf Brenner of University of Ulm in a commentary published with the study.
Despite these caveats, Rotter and Brenner see the current results as promising, particularly since there is a growing need to develop an effective therapy to repair cartilage damage as people live longer.
"We think that the technology might be viable for the older age group, which is of utmost concern," Rotter said in an email.
Repairing painful knees
While different cartilage repair techniques have been developed, "no gold standard has been established," Rotter and Brenner note. When it comes to developing a cell-based therapy, such as the one used in the current study, they say possible problems include "locating the most suitable cell source" and "minimizing negative effects of tissue harvest."
"The fact that after two years the composition of the cartilage is closer to native than after six months is already a great achievement, which makes the proposed treatment highly promising," said Martin.
Jevsevar, though, wondered if the results would "hold up over time." He said that similar technologies have been tried, such as harvesting and then growing knee cartilage cells in a test tube and then implanting them into the knee.
They do OK, said Jevsevar.
"The problem with the types of technologies that have been out there so far is none of them have done a good job of standing up to the test of time," said Jevsevar. "So it looks like really good normal cartilage (initially) and slowly it begins to change over time."
Explaining that there must be some unknown factor going on, he said just two years of good results is still too little time to judge.
"We want to see five years or 10 years," said Jevsevar. "If it was your knee, you'd want to know that. If it were an operation that would only work for two years, you may choose to do it, but probably you wouldn't."