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.
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Last month, TiGenix announced as yet unpublished results of a randomized clinical trial in which ChondroCelect outperformed a conventional treatment -- meant to repair, not restore -- called microfracture.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."
Plug the gap
One minute Jean Roso of Diamond Bar was carrying her dog downstairs after his bath. The next minute she was on her way to the emergency room.
The 44-year-old hair stylist blames her teenage years filled with gymnastics and dance more than she blames Cooper, her 35-pound mutt.
"That was a lot of wear and tear on my poor knees," says Roso, now 44.
Mirzayan is Roso's doctor, too, but for her he used a different procedure, implanting a calcium sulfate plug into her damaged right knee.
It's not at all new to ream out a damaged section of a patient's knee and implant a plug, but in the past this was a plug made of actual cartilage and bone -- either from the patient (an osteochondral autograft) or from a cadaver (an osteochondral allograft).
But fitting that sort of plug perfectly can be very difficult. "Plus, an autograft is like robbing Peter to pay Paul," Mirzayan says. Although the plug is taken from a part of the knee that bears little weight, cutting it out still introduces a new hole, and thus a new weakness. With an allograft, on the other hand, there's the possibility of introducing disease or infection.
The calcium sulfate plug Roso received -- called a TruFit plug and made by the OsteoBiologics division of London, England-based company Smith & Nephew -- is based on quite a different idea: providing a scaffold for new cartilage and bone to grow into.
Again, this is a difficult claim to test. But the University of Louisville's Caborn, who in October 2003 was the first to perform one of these implants, has had several opportunities to do "second-look arthroscopies" and has been happy with what he's found: bone growing where there should be bone, and cartilage where there should be cartilage. And the tests he's performed have shown that, as desired, it's articular cartilage, not fibrocartilage.
Just the other day -- almost exactly a year after the surgery on her knee -- Roso took a couple of jogging steps on the way to her mailbox, and discovered, "I can actually run on it."
Researchers at the Cleveland Clinic in Ohio are experimenting with a different sort of scaffold: collagen from rat tails. As in the Carticel procedure, a doctor takes chondrocytes from a healthy part of a patient's knee. But in this ACI, the chondrocytes are grown in the rat tail collagen, which is then cut to fit the patient's lesion and implanted.
Because collagen is one component of articular cartilage, the scaffold can actually be incorporated into the tissue growth -- instead of dissolving, the way a TruFit plug does. And because the process is quicker than the Carticel process, the chondrocytes are used earlier in their lifespan, when they're more likely to remain true to cartilage form, says Dr. Anthony Miniaci, an orthopedic surgeon and head of the Cleveland Clinic's sports medicine department.