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Relieving knee pain: Doctors use a patient's cultured cartilage cells to repair certain injuries

By Tammie Smith

Mar. 27, 2008 (McClatchy-Tribune Regional News delivered by Newstex) --
The slender vial, about the length of a thimble, held about 12 million laboratory-grown knee cartilage cells clustered at the bottom in a clear solution.

Technician Andrea Smith used a syringe to draw up the cells, which when jiggled with a pipette turned the clear solution a cloudy white. She handed the syringe to Dr. Kenneth Zaslav.

Zaslav, an orthopedic surgeon and sports-medicine doctor, had spent the past hour preparing an area on the cartilage of the patient's left knee that had worn away. A lesion, or scar, that had formed was causing the patient debilitating knee pain.

Using a scalpel, Zaslav scraped away the bad cartilage and removed a small margin of surrounding cartilage, leaving an area of white, smooth, healthy cartilage.

Next, stitch by stitch, much like hand sewing on a tiny pocket, Zaslav attached a precisely measured patch of collagen over the prepared area, leaving a tiny opening at the top. A special biological glue was applied around the edges of the collagen patch.

The patch was checked for leaks by squirting a solution into the opening. The same syringe was used to remove the saline.

About an hour into the surgery, it was time to transplant the cartilage cells.

Weeks earlier, a snippet of healthy cartilage had been arthroscopically removed from an area of the patient's knee that does not bear much weight. The tissue was packaged in a special kit and shipped to the biotechnology company Genzyme Corp. (NASDAQ:GENZ)

Over the course of a few weeks, a Genzyme Tissue Repair lab grew millions more of the patient's cells and shipped them back to St. Francis Medical Center for the March 14 surgery. Genzyme calls its knee cartilage product Carticel.

"They are now chondroblasts, cells that turn into cartilage," Zaslav said as he inserted the syringe through the tiny opening and released the cells.

"The entire process to get articular cartilage similar to what the patient has in the rest of knee is a year," Zaslav said. "By six months, they have a soft version of cartilage. It takes up to two years for the full maturation."

For the patient, who agreed to have the surgery photographed but did not want to be identified, the surgery was another attempt to find relief from knee pain. During the next months, doctors hope the cells will further multiply and form new cartilage.

"There are lots of thing we have perfected," Zaslav said. "One of the most difficult things has been to repair cartilage. If you cut your skin, new skin forms. When you break cartilage, there is no genetic ability for new cartilage to form."

So researchers are looking for ways to grow it in laboratories and transplant it to patients. Carticel, on the market for more than a decade, is the leader of the pack. Other efforts are looking at loading the cartilage cells into a bioabsorbable patch and then placing it. Another effort is studying an injectable hydrogel.

Only in the past several years have results of longer-term follow-up studies of Carticel been available, and they suggest that benefits can last as long as a decade for some patients. The surgery remains recommended for a select group of patients. Typically, they have to have failed previous procedures.

The studies on the effectiveness of Carticel include:

--An observational study presented this month at a national meeting of orthopedic surgeons. Researchers reported on a multicenter trial that tracked the experiences of 72 patients for an average of 9.2 years after surgery. At one to five years follow-up, 54 of the 72 participants reported improvement, and nine showed no improvement. The procedure failed in nine cases.

At six to 10 years follow-up, the number showing improvement was 50, the number not improved 10 and the number of failures was 12.

--An earlier study, the Study of the Treatment of Articular Repair, followed 154 patients over four years. Patients were enrolled at 29 sites. All had undergone a previous knee surgery that failed to cure their pain.

Four years into the study, 101 patients described their knee function as "good," the midpoint on a scale that ranged from poor to excellent. At that point, 37 patients were classified as failing treatment. Many patients needed additional procedures on the treated knee.

In the studies, most patients were male, the average age was 35 to 37, and most had undergone a previous cartilage-repair procedure. Knee replacements, which typically last 10 to 20 years, are not considered a good option for younger patients.

To date, more than 14,000 people have had Carticel surgery, which is marketed as a treatment for cartilage damaged from such overuse injuries as those seen in runners or from injuries resulting from accidents.

It is not a treatment for generalized knee osteoarthritis, which often comes with age and with years of carrying excess weight. Complications can include tissue overgrowth that could require further surgery.

Julia Smith turned to Carticel four years ago after a previous surgery in 1995 did not give permanent results.

"My kneecap was not tracking the way it should be. It kept hitting my femur," said Smith, a competitive runner. "That is what was causing cartilage damage."

Smith had Carticel surgery at the same time she had surgery to have her lower legs operated on to correct an alignment problem that contributed to the cartilage injury.

"I was riding my bike in six months. I did a 100-mile bike ride six months after surgery," Smith said.

It was a year before she could run again. She is now back running about 30 miles a week and has beaten her time in some competitive races she has won.

"I am pain-free," Smith said. "I am back doing what I was doing before -- and better."

Contact staff writer Tammie Smith at TLsmith@timesdispatch.com or (804) 649-6572.

Newstex ID: KRTB-0177-24060920

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