A grow-your-own-cartilage procedure, obviating total kneereplacement, reports partial success in the New England Journal ofMedicine (NEJM) issue published today. Results were even betterin repairing thigh-bone joints.Swedish orthopedic surgeon Lars Peterson and cell biologist AndersLindahl at the University of Gsteborg took small helpings (300 to500 milligrams) of healthy chondrocytes (cartilage cells) from theknees or femurs of patients with damaged joint surfaces and grewthem up in culture for 14 to 21 days. By that time, the original185,000 to 455,000 cells had multiplied to 2.6 million to 3.0million. These they implanted by open-knee surgery to resurface thesmooth areas roughened or destroyed by accident DD especiallysports trauma DD or disease.With exercise, full weight-bearing use returned during the first eightweeks after surgery.The NEJM paper, titled "Treatment of Deep Cartilage Defects inthe Knee With Autologous Chondrocyte Transplantation," actuallyreports femoral treatment as well. Peterson is principal authorAlong with his university appointment, he is clinical director of theG¿teborg Medical Center, a private athletic trauma clinic.Now the Swedes have joined forces with BioSurface TechnologyInc., a Cambridge, Mass., company that specializes in human cellculture, including chondrocytes. BioSurface itself is due to beacquired before year's end by its Cambridge neighbor, GenzymeCorp. (See BioWorld Today, July 26, 1994, Page 1.)Market Roll-Out Next YearThe president and CEO of BioSurface, David Castaldi, toldBioWorld, "To the best of my knowledge, no other group in theworld besides the Peterson-Lindahl team, has put transplanted, lab-grown chondrocytes into humans." He added that the other majorplayer in the field is Advanced Tissue Sciences Inc., of La Jolla,Calif. This firm, like BioSurface, has cartilage replacement on itsresearch agenda, but so far emphasizes cultured skin celltransplantation.BioSurface has been collaborating with the Swedes for the past twoyears, Castaldi said. One of their joint research goals is to deliverthe expanded cell population to the affected site by arthroscoperather than open-knee surgery."In working with them, we believe we have a significant lead on thedevelopment of the cultured chondrycyte product, he said. In fact,we are planning a limited market roll-out of the cartilage-cells inEurope the second half of 1995, and in the U.S. by the end of thatyear, or soon after."The Swedish-American partnership plans to start its market entry byproviding the cells to selected top academic orthopedic centers,Castaldi said, "in a way that will ensure they know how to use theproduct well, before we roll it out more broadly.""We are in a good situation," Peterson told BioWorld Today. "Ifanybody in America wants to try this procedure, they have to havesome help with chondrocyte culture. What BioSurface can do isoffer that help in a very professional way."Users will harvest healthy chondrocytes from their patients, andship them to the BioSurface laboratory in Cambridge foramplification in culture. This will be a commercial pay-for-serviceundertaking rather than a clinical trial, as the G¿teborg data thatNEJM released today should satisfy European requirements.As for the planned market introduction in the U.S. late next year,Castaldi said he expects that the FDA will not require clinical trialdata, as the chondrocyte product derives entirely from the patient'sown cells. When BioSurface introduced its autologous skin-graftcells to treat burn injuries, the FDA did not demand trial data, henoted.BioSurface has two pending patents, with other applications in thepipeline, Castaldi said.Cartilage tissue does not normally regenerate in the body. Defectiveknee joints cause pain, swelling, limited movement, and can "lock."Lesions tend to degenerate into osteoarthritis, which calls for totaljoint replacement. In the U.S., an estimated 170,000 total kneereplacements were performed last year. At best, these prosthesesdeteriorate with time.Seven of the 23 Swedish patients described in the journal articlereceived the cultured chondrocytes to repair a diseased or injuredpatella (knee joint). They ranged in age from 17 to 32, and had beensuffering for three to 10 years from full-thickness cartilage defects1.6 to 6.5 square centimeters in size.In follow-ups from 16 to 66 months, the NEJM article reported, allpatients experienced reduced swelling, pain and crepitus(crackling), with no knee-locking. But longer-term patellar-transplant results were "disappointing.""We have now treated close to 90 patients," Peterson said, "and ourresults are improving all the time."Only one patient, a 27-year-old woman who had incurred herpatellar defect at age 17, achieved an "excellent" outcome of thecultured-cell treatment, rated 5.5 years after the intervention. Shewas among the first patients the Peterson-Lindahl team treated, in1987. Today, Peterson said, she continues to do well nearly sevenyears later.Four other patellar patients had "fair" to "good" results, and twofailed cases required repeat operations, because of central wear onthe transplants, with pain and locking."We can do better," Peterson confided, "specifically on the patellarsurface, treating a larger area. And we don't any longer see thelimitation of age as a contraindication. We know now that we canculture cells at a higher age than before."Femur Lesions TreatedLesions on the femur did better. Of 16 patients treated (nine men;seven women), six received "excellent" report cards; eight, "good."The remaining two needed repeat cell-replacement surgery.One of the femoral cases, a 22-year-old woman required re-operation because she sustained an unrelated knee injury. At the endof 46 months, she received an "excellent" rating.Peterson, Lindahl et al. began their paper in NEJM by quoting thegreat 18th-century English physician, William Hunter (1718-83):"From Hippocrates to the present age it is universally allowed thatulcerated cartilage is a troublesome thing and that, once destroyed,is not repaired." They expect transplantation of culturedchondrocytes to abrogate this age-old truism.Addressing himself to the biotechnology community, Peterson toldBioWorld, "I would say this is an example of a new area ofcooperation between cell biologists and clinicians _ orthopedicsurgeons. It opens up areas not only for cartilage but probably in thefuture for other musculoskeletal tissues." n
-- David N. Leff Science Editor
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