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When knees can't take any more

Medicine | IN THE LAB

Biotechnology is tackling worn-out cartilage with cell culture, artificial plugs and growth factors to coax the knee to heal.

March 12, 2007|Karen Ravn | Special to The Times

WE count on them to be strong and supportive, flexible and accommodating, willing to go the extra mile even when we load them down more than we should.

Our knees. We put them through their paces, so to speak, every day. No wonder that, every now and then, they fall down on the job.

Treatments for needy knees generally fit into three categories, says Dr. David Caborn, professor of orthopedic surgery at the University of Louisville: relief (treating the symptoms); repair (getting things back in working order, if not back to normal); and, most recently, restoration (trying to return a damaged knee to its original condition).

In particular, researchers these days are looking for ways to make damaged cartilage as good as new again -- and they're getting closer and closer to pulling it off.

Articular -- or hyaline -- cartilage is the firm, shiny, slick tissue that protects the ends of the thigh bone and the shin bone. Its nearly frictionless surface allows the bones to glide past each other smoothly even when the knee is carrying around a lot of weight.

But strong as it is, articular cartilage -- unlike the bones it safeguards -- has no blood supply of its own, leaving it helpless when it gets hurt. A cut in the skin will heal itself, but a tear in articular cartilage will not.

That's where scientists are stepping in to help.

"We're going through a very exciting time in the whole world of cartilage regeneration," says Dr. Bert Mandelbaum, vice president of the International Cartilage Repair Society and team physician for the U.S. soccer team and for Pepperdine University.

Advances are being made in three main areas: manipulating cartilage cells, or chondrocytes; developing scaffolds for new tissue to grow on; and using growth factors to hurry things along.

"The holy grail will be to have all three come together," Mandelbaum says. "We need to integrate all three into a lunar excursion module. That's how we'll get to the moon."

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Cell culture

In 2005, Miguel Rueff of Rialto would feel fine after his weekly softball and basketball games. But his left knee would swell up, and he felt some unidentified floating objects that didn't use to be there.

Those objects were broken-off pieces of cartilage that had left behind two lesions, or holes, says Rueff's doctor, Raffy Mirzayan, co-director of sports medicine and director of cartilage restoration and repair at Kaiser Permanente in Baldwin Park.

Mirzayan treated Rueff, now 28, with an autologous chondrocyte implantation, or ACI, using a method called Carticel, developed by Genzyme Corp. in Framingham, Mass.

In this procedure, a surgeon takes a raisin-size sample of healthy articular cartilage from a patient's knee and sends it to Genzyme's laboratory. There, the 200,000 to 300,000 chondrocytes originally contained in the sample are grown (using a proprietary process) until there are about 12 million.

The surgeon then injects these 12 million cells into the patient's lesion under a patch of tissue he makes from the periosteum, the lining of the patient's shin bone. The company says these cells "mature and eventually fill the defect with a durable cartilage with properties similar to original cartilage."

It's hard to check and see, of course. As Mirzayan says, patients aren't eager to have another surgery just for the sake of science.

But Rueff is happy with his results. "Last week was my first basketball game since the surgery," he says. "I actually felt great."

Genzyme introduced Carticel in 1995. TiGenix, a biomedical company in Belgium, now hopes to take such cellular technology to the next level with a new product called ChondroCelect that is not yet approved for use.

The idea behind ChondroCelect is not to settle for any old chondrocyte in the implantation procedure, but rather to select the chondrocytes most likely to be good hyaline cartilage when they grow up.

Gil Beyen, chief executive of TiGenix, says that when cultured chondrocytes multiply, they have a tendency to forget who they are. "They become more like stem cells" -- very susceptible to outside influences and apt to turn into the wrong kind of cells.

For example, if they're injected into muscle tissue, some of them will turn into muscle. Only the ones "with a mind of their own" will persist in becoming cartilage.

Beyen says ChondroCelect favors these strong-minded chondrocytes over the go-with-the-flow ones. "The way we culture the cells leads to better cartilage than other products like Carticel," he says.

Last month, TiGenix announced as yet unpublished results of a randomized clinical trial in which ChondroCelect outperformed a conventional treatment -- meant to repair, not restore -- called microfracture.

In microfracture a surgeon drills tiny holes into the bone, which gradually fill up with fibrocartilage, a kind of scar tissue. This may provide temporary relief, Mirzayan says, "but it's definitely different from the hyaline cartilage we're born with. The main difference is, it doesn't last as long."

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Plug the gap

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