Blue-Collar Cell Therapy

Among high-concept forms of medicine, few approaches have as much intuitive appeal as cellular therapy. The idea is disarmingly simple-remove homegrown cells from the patient’s body, grow them to vast numbers in the lab and then give them back as medicine. It has already been attempted in a few instances against cancer. Remember the TIL cell-“tumor infiltrating lymphocytes”-craze of the 1980s?

But perhaps the most interesting cellular therapy to date, and the only one to receive the blessings of the Food and Drug Administration as a bona fide biologic intervention, involves not one of the body’s vaunted cellular paladins, such as lymphocytes or neurons, but rather a blue-collar cell known as the chondrocyte. These cells provide the cushion known as cartilage between joints, and for the past three years, orthopedic surgeons in this country and Europe have been using them to rebuild knee joints denuded of cartilage by acute or repetitive trauma.

Like many new technologies, this one had a fitful and peripatetic evolution. The initial idea was explored in the early 1980s by a group of surgeons at the Hospital for Joint Disease in New York, including Mark Pitman and a visiting surgical colleague, Lars Peterson. They reported preliminary results in 1984 of cartilage implants in rabbits.

Peterson returned to the University of Goteborg in his native Sweden, where he hooked up-at the suggestion of a tennis partner-with Anders Lindahl, an expert in cell culture. The team ultimately developed a method for culturing cartilage cells and implanting them in humans and received approval to perform the first human implant in 1987, using a technique that is now being taught to more than 2,000 orthopedic surgeons in this country. (The Cambridge, Mass.-based Genzyme Corp. became involved in 1995 when it acquired another company, BioSurface Technology, which was also working on the technology.) The Food and Drug Administration approved the treatment method in August 1997.

At the present time, regulatory approval is limited to procedures that treat the part of the femur (the long bone of the thigh) that meets the knee. When the knee joint is damaged, either in an acute injury such as a skiing accident or by more gradual wear and tear, the cartilage lining the thigh bone where it joins the knee often becomes damaged. This tissue rarely regenerates, and the erosion announces itself with locking, catching, swelling and pain.

According to the procedure developed by Peterson, surgeons harvest a tiny snippet of healthy cartilage arthroscopically. This biopsy sample-about the size of a thumbnail clipping, according to Ross Tubo of Genzyme Tissue Repair, a subsidiary of Genzyme-is then sent to a cell culture laboratory. This bit of tissue, a mere 100 to 200 milligrams, is roughly 99 percent cartilage and 1 percent chondrocytes, the cells that actually make cartilage. So the sample must be digested to separate the cells from the matrix before the cells can be cultured.

After some three or four weeks, there are enough cells for an implant-roughly 30 million cells per milliliter of fluid. They are sent back in vials to the orthopedic surgeon, who performs traditional methods of knee surgery to insert the cells (researchers are also working on ways to deliver the cells by arthroscope).

Genzyme Tissue Repair began to market the cell-culturing service, which they call Carticel, in 1995. Since that time, more than 1,000 patients have been treated with a joint-restoring medicine that in a sense is of their own making. The procedure is not cheap: Genzyme estimates that the average cost is about $26,000. But the company has mounted a vigorous effort to get insurance companies and health maintenance organizations to reimburse the operation.

Sometimes the transplanted cells work too well. The most frequent side effect appears to be what is known as tissue hypertrophy-an excessive growth of cartilage. In one follow-up study, 43 percent of the patients had some degree of excess tissue growth in the implanted joint. On the other hand, early data suggest that the technique is in many cases quite successful for the optimal patient population-those between 15 and 50 years of age.

And the treatment appears to be durable. In a recent presentation to the American Academy of Orthopedic Surgeons, Lars Peterson reported that in a group of 38 patients who received a cartilage-cell transplant more than five years ago, 31 patients were judged to have had a good-to-excellent result two years after the procedure, and of those, 30 continued to show good-to-excellent results five years after.

Peterson has already applied the basic technique to patients with ankle and shoulder injuries in Sweden, and perhaps it’s only a matter of time before the phrase “autologous cultured chondrocytes” will trip mellifluously off the tongue of ESPN anchormen as they describe the cellular rescue of one more superstar fetlock. “I don’t know of any professional athlete that has used the procedure,” says Tubo, “but it certainly would be applicable to a career-threatening injury where you have a pothole in the middle of your cartilage.”