Correspondence
Autologous Chondrocyte Transplantation
N Engl J Med 1995; 332:539-540February 23, 1995
- Article
To the Editor:
Brittberg et al. (Oct. 6 issue)1 are to be commended for conducting a study of 23 patients that not only involved the transfer of articular and nonarticular tissue into deep cartilage defects in the knee but also required two follow-up operations. In the second of those procedures, biopsy specimens extending to the subchondral bone were taken from the central part of the transplant.
In consideration of these factors, it is perhaps understandable that no control group was included in the study. Nevertheless, it would have been nice to know just how much benefit was derived from the substantial effort devoted to the harvesting, isolation, culture, and reinjection of the chondrocytes. Such information might have been obtained had, for example, some patients been randomly assigned to treatment with transplanted periosteum without cultured chondrocytes.
Treatment of articular defects has been successful in preclinical studies that used periosteum without chondrocytes,2,3 that used periosteum with chondrocytes,4 and that excluded periosteum but used endogenous cells.5
5 ReferencesStephen B. Trippel, M.D.
Massachusetts General Hospital, Boston, MA 021141
Brittberg M ,Lindahl A ,Nilsson A ,Ohlsson C ,Isaksson O ,Peterson L . Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331:889-895
Full Text | Web of Science | Medline2
O'Driscoll SW ,Salter RB . The repair of major osteochondral defects in joint surfaces by neochondrogenesis with autogenous osteoperiosteal grafts stimulated by continuous passive motion: an experimental investigation in the rabbit. Clin Orthop 1986;208:131-140
Web of Science | Medline3
Rubak JM ,Poussa M ,Ritsila V . Chondrogenesis in repair of articular cartilage defects by free periosteal grafts in rabbits. Acta Orthop Scand 1982;53:181-186
CrossRef | Medline4
Grande DA ,Pitman MI ,Peterson L ,Menche D ,Klein M . The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 1989;7:208-218
CrossRef | Web of Science | Medline5
Hunziker EB, Rosenberg LE. Induction of repair in partial thickness articular cartilage lesions by timed release of TGFβ. In: Transactions of the 40th Annual Meeting of the Orthopaedic Research Society, New Orleans, February 21–24, 1994. Rosemont, Ill.: Orthopaedic Research Society, 1994:19:236. abstract.
To the Editor:
The patients described by Brittberg et al. were evaluated with a four-grade system based on the presence or absence of pain, swelling, and locking. Were the qualitative terms for the four grades provided by clinicians or based on assessments by the patients? A patient's idea of what constitutes a good or excellent result may be completely different from that of a physician. For example, a patient who had “mild aching with strenuous activity but no swelling or locking” after surgery might have judged the result to be poor rather than good, which was the grade Brittberg et al. gave for this result. Evaluating a surgical procedure in an uncontrolled and unblinded fashion, with a scale developed and rated by clinicians, could have led to a biased assessment of success.
James G. Wright, M.D., M.P.H.
Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaAuthor/Editor Response
The authors reply:
To the Editor: The treatment of deep cartilage defects in the knee was based on a rabbit model in which a deep chondral lesion in the patella was covered with periosteum, and autologous chondrocytes were injected below it. A similar defect in the other knee, which was only covered with periosteum, served as a control. There was significantly better tissue repair at the sites seeded with chondrocytes than at the sites that were treated only with periosteum.1,2 In the experiments mentioned by Dr. Trippel, periosteum was used to treat osteochondral defects extending down to cancellous bone.3 The subchondral bone marrow cells, as well as cells in the cambium of the periosteum, have a chondrogenic potential that could contribute to tissue repair. In our rabbit experiments, there was no opening of the subchondral bone plate. The control knee had significantly less repair.
Knee symptoms in patients with single, isolated cartilage defects should be distinguished from symptoms in patients with osteoarthritis, which is characterized by widespread cartilage wear and joint dysfunction. There are no good evaluation systems for the first group of patients, but there are some for patients with osteoarthritis. In our pilot study, we used a simplified evaluation of common symptoms in patients with isolated cartilage defects (i.e., locking of the knee, localized pain, and swelling). The symptom that the patients could tolerate least was locking, followed by pain. Locking was the key element in judging the outcome of surgery. As long as the patient had no locking, he or she was satisfied with the results.
We agree with Dr. Wright that there is a risk of bias in the assessment of success in uncontrolled studies. We performed a pilot study of autologous chondrocyte transplantation in patients with isolated, symptomatic chondral lesions. Clinical studies with periosteal4 as well as perichondral5 grafting have also been uncontrolled. The next step is to determine the extent to which chondrocytes contribute to the repair of chondral lesions in the knee. A multicenter, randomized, controlled study is scheduled to start this year. Several different evaluation systems, with unbiased preoperative and postoperative assessments, will be used.
5 ReferencesMats Brittberg, M.D.
Anders Lindahl, M.D., Ph.D.
Lars Peterson, M.D., Ph.D.
University of Göteborg, S-413 45 Göteborg, Sweden1
Brittberg M, Lindahl A, Nilsson A, Peterson L, Isaksson O. Healing of injured rabbit articular cartilage after transplantation with autologously isolated and cultured chondrocytes. In: Abstracts of the Bat Sheva Seminars on Methods Used in Research on Cartilaginous Tissues, Tel Aviv, Israel, March 16–26, 1989. Nof Ginnosar, Israel: Bat Sheva, 1989:28-29. abstract.
2
Grande DA ,Pitman MI ,Peterson L ,Menche D ,Klein M . The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res 1989;7:208-218
CrossRef | Web of Science | Medline3
O'Driscoll SW ,Salter RB . The repair of major osteochondral defects in joint surfaces by neochondrogenesis with autogenous osteoperiosteal grafts stimulated by continuous passive motion: an experimental investigation in the rabbit. Clin Orthop 1986;208:131-140
Web of Science | Medline4
Hoikka Vej,
Jaroma JH ,Ritsila VA . Reconstruction of the patellar articulation with periosteal grafts: 4-year follow-up of 13 cases. Acta Orthop Scand 1990;52:36-395
Homminga GN ,Bulstra SK ,Bouwmeester PS ,van der Linden AJ . Perichondral grafting for cartilage lesions of the knee. J Bone Joint Surg Br 1990;72:1003-1007
Web of Science | Medline
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Brunella Grigolo, Gina Lisignoli, Anna Piacentini, Mauro Fiorini, Pietro Gobbi, Giovanni Mazzotti, Manuela Duca, Alessandra Pavesio, Andrea Facchini. (2002) Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF®11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials 23:4, 1187-1195
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Brunella Grigolo, Livia Roseti, Mauro Fiorini, Milena Fini, Gianluca Giavaresi, Nicolò Nicoli Aldini, Roberto Giardino, Andrea Facchini. (2001) Transplantation of chondrocytes seeded on a hyaluronan derivative (Hyaff®-11) into cartilage defects in rabbits. Biomaterials 22:17, 2417-2424
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