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Autologous Chondrocyte Transplantation

  • Authors: Vladimir Bobic, MD
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Target Audience and Goal Statement

This activity is intended for orthopaedic surgeons and pharmacologists.

The goal of these activities is to define "state-of-the-art" treatment protocols and clinical strategies for the diagnosis and management of bone and joint disorders, to enhance the care of patients with arthritis and degenerative diseases and to support quality clinical practice of orthopaedic surgeons involved in their care.

Upon completion of this activity, participants will be able to:

  1. Describe the correlation between patellar disease and post-operative anterior knee pain.
  2. Discuss the contraindications of TKA in young patients with DJD.
  3. Review the relationship between knee instability and partial absence of meniscal tissue on accelerated wear of articulating surfaces.
  4. Identify pseudoanaplastic bone tumor features which predict long-term survival after aggressive management of renal cell cancer metastasis.


  • Vladimir Bobic, MD

    Consultant Orthopaedic Knee Surgeon, Rluh Liverpool, Broadgreen Hospital Knee Service, Liverpool, England.

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  • Medical Education Collaborative, Inc. has assigned 1 contact hour (0.10 CEUs) of continuing pharmaceutical education credit. ACPE provider number: 815-999-00-021-H04. Certificate is defined as a record of participation.

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Autologous Chondrocyte Transplantation

Authors: Vladimir Bobic, MDFaculty and Disclosures


New Methods for Repairing Articular Cartilage Damage


Numerous studies confirm the correlation of the knee instability and partial absence of meniscal tissue on accelerated wear and tear of articulating surfaces. It is well known that the capacity of articular cartilage for repair is limited. Partial-thickness defects in the articular cartilage do not heal spontaneously. Injuries of the articular cartilage that do not penetrate the subchondral bone do not heal and usually progress to the degeneration of the articular surface.

Autologous chondrocyte implantation and transforming growth factors have substantial treatment potential at the cellular level. The chondrocytes are the metabolic power plants that produce the extracellular matrix. Once chondrocytes mature or differentiate, their capacity to reproduce slows down, but they continue with their metabolic activities.

Current state of the art of articular cartilage repair is the result of the increased awareness of the importance of articular cartilage damage, the explosive interest, the intense research, and rapid development of clinical applications.

Autologous chondrocyte transplantation (ACT) is one of the first orthopaedic biotechnologies that is already clinically available and approved by the Food and Drug Administration (FDA). The Swedish clinical experience with ACT now extends to more than 800 patients, including 200 patients with a minimum follow-up of 2 years.


Study and Results

Among the series of ACT papers presented today, Lars Peterson and colleagues[1]assessed the response to treatment at 2 years, and the subsequent durability of the repair in the intermediate to long term (5-11 years). Two hundred nineteen patients underwent ACT between 1987 and 1996, 213 of whom were assessed with 5 rating scales. Forty-six patients consented to arthroscopic second-look evaluation, 19 patients to the harvest of tissue from the repair site, and 14 patients underwent electromechanical indentation probe testing. Defects evaluated were located on the femoral condyle (57), femoral condyle with anterior cruciate ligament (ACL) repair (27), osteochondritis dissecans (32), patella (32), trochlea (12), and multiple lesions (53). Patients averaged 2 previous surgeries to the affected knee. The Cincinnati rating score was used, and good to excellent results were achieved in 90% , with femoral condylar lesions, 74% in femoral defect with concomitant ACL reconstruction, 84% in osteochondritis dissecans, 69% in patellar lesions, 58% in trochlear lesions, and 75% in multiple lesions of patients.

Outcomes were dependent on strict attention to alignment in patients with patella defects, and size of defect in trochlear lesions. Thirty-one patients graded good to excellent at 2 years were re-evaluated in the 5- to 10-year period (mean, 7.5 years), demonstrating 96% durability as measured by a rating of good/excellent maintained from 2 years to 5- to 10-year follow-up. Histologic evaluation found hyaline-type repair tissue in 74% of patients with at strong correlation (0.73) between hyaline repair tissue and good/excellent results.

Treatment of chondral and osteochondral lesions with ACT appears to produce new tissue similar in histologic and mechanical characteristics to hyaline cartilage, resulting in good clinical outcomes in more than 75% of patients. Results are best in lesions of the distal femur, including multiple defects. Patellar lesions require strict attention to alignment, and trochlear results are size-dependent.


Studies Show Pain Relief and Improved Function Following ACI on Lesions


Autologous cultured chondrocyte implantation (ACI) was first introduced in Sweden in 1987 and has been used clinically in the United States since 1995. The author reported on the international, multicenter experience with ACI, including outcomes in 40 patients evaluated 36 months postimplantation (ACI 1999 Registry, data collected in 1998).[2] Patients were prospectively monitored and evaluated preoperatively (at time of biopsy) and at 12, 24, and 36 months using a standardized knee examination and the modified Cincinnati Knee Rating System completed by both treating clinician and patient.

Adverse events, operative procedures following ACI, and treatment failure data were collected using standardized forms for all patients. Five hundred eighty-three international centers provided preoperative data including demographics and lesion characteristics. Patients averaged 35 years of age, with 97% between the ages of 15 and 55 years. Seventy-one percent had undergone previous surgery on the affected knee, including 59% who had failed one or more treatments for articular cartilage injury (eg, drilling, abrasion, microfracture). Results for all lesions, including tibia and patella, at 36 months demonstrate improvement in 74% of patients by clinician evaluation, and 77% when patients self-evaluated. Results were best in lesions on the distal femur, with 85% improving by both clinician and patient evaluation. Using the modified Cincinnati Knee rating system, clinician and patient evaluations of overall knee condition were improved from a poor/fair baseline score of 3.10 ± 1.11 SD/2.97 ± 1.33 to a good/very good evaluation of 6.77 ± 2.87 SD/6.61 ± 2.91, respectively. Pain, swelling, partial and full giving way, stiffness, catching, and locking were all significantly improved. Many patients had previous surgery and several concomitant procedures.

The multicenter results presented in this paper appear to parallel the Swedish experience and demonstrate a durable repair out to 36 months. ACI appears to be an efficacious and safe treatment for full-thickness chondral lesions of the femoral condyles and trochlea.


Osteochondral Grafts Improve Symptoms, but May Increase Risk of Osteoarthritis

The aim of this study is to evaluate long-term results of osteochondral grafting in the knee joint.[3] Authors treated 35 patients with severe osteochondral defects with autologous osteochondral transplantation, between 1986 and 1992. The large cylindrical grafts were harvested from the posterior part of the medial or lateral femoral condyle. The majority of patients (27) suffered from osteochondrosis dissecans, 8 patients presented with post-traumatic osteochondral defects. Twenty-nine patients were included in the follow-up. In 12 patients, the transplanted knees have been graded as normal (grade I according to the ICRS standard cartilage evaluation form). Fourteen knees have been graded as nearly normal (grade II). Three patients with a varus malalignment presented with unsatisfactory result (grade III). No patient was assessed with severely abnormal (grade IV). The great majority of patients improved their activity level. However, 12 patients developed new radiological signs of osteoarthrosis with a decrease in the radiological score of Kellgren and Lawrence about one stage.

The authors concluded that autologous osteochondral transplantation is an effective method in the treatment of severe osteochondral defects that can improve symptoms in the majority of patients. However, Dr. Laprell expressed a concern about the increase of radiological signs of osteoarthritis at the latest follow-up.


Study Examines Effects of Intermittent High Loads on Articular Cartilage


The response of articular cartilage to forms of exercise that involve intermittent high loads across the joint is poorly understood. The authors hypothesize that resistance training injures articular cartilage in a histologically detectable pattern. The purpose of this study was to establish a new animal model in which the knee joint is intermittently loaded and to histologically evaluate the effect on articular cartilage. Specimens from experimental animals showed articular cartilage damage following a weighted leg press exercise. The severity of injury in the control group was significantly less than that of the experimental group.

The authors reported that intermittent high load resistance training causes morphological changes in rat articular cartilage.[4] Existing animal models for articular cartilage injury utilize low-intensity exercise, such as running or surgically induced injury. This new animal model will be useful in understanding the mechanisms by which the development of osteoarthritis occurs as a consequence of high intensity training.


Treatment of Unstable Meniscal Tears Affected by Articular Cartilage Degeneration


A primary goal in considering treatment for meniscal injuries is maintaining healthy articular cartilage, yet the chondroprotective effects of various meniscal injury treatments are unknown. The purpose of this study[5] was to compare the degenerative effect on articular cartilage caused by either an unstable meniscus tear or, a common treatment for this type of tear, a partial meniscectomy. Authors used a canine model to quantify medial femoral condyle cartilage degeneration resulting from a surgically created medial meniscus bucket-handle tear or a partial meniscectomy of the same region (each group, n = 10). After sacrifice at 12 weeks, gross chondropathy and cartilage stiffness were assessed from cartilage adjacent to the meniscal insult. Gross chondropathy was greater compared with unoperated controls in both experimental groups, with partial meniscectomy causing significantly more chondropathy. Cartilage tensile stiffness was significantly lower than unoperated controls by nearly 28% in both the bucket-handle tear and partial meniscectomy groups, but no difference was observed between these experimental groups. Additionally, the severity of gross chondropathy was found to significantly correlate with the decrement in tensile stiffness properties of the articular cartilage.

The authors indicated that significant degeneration of canine articular cartilage develops to a similar degree in the presence of a partially healed meniscal tear or a partial meniscectomy of the same region. This information may be useful to the orthopaedic surgeon choosing treatment for an unstable meniscal tear. The authors conclude that because articular cartilage degeneration has limited healing potential, the effects on adjacent cartilage caused by various meniscal therapy should be carefully considered.


  1. Peterson L, Lirdahl A, Brittberg M, Nilsson A. Durability of autologous chondrocyte transplantation of the knee. In: Program and abstracts of the 67th annual meeting of the American Academy of Orthopaedic Surgeons; March 15-19, 2000; Orlando, Fla. Paper No. 125.
  2. Mandelbaum B, Browne J, Ergglet C, Fu F, Micheli L, Moseley JB. 3-year multicenter outcome of autologous chondrocyte implantation of the knee. In: Program and abstracts of the 67th annual meeting of the American Academy of Orthopaedic Surgeons; March 15-19, 2000; Orlando, Fla. Paper No. 126.
  3. Laprell HG, Petersen W. Long-term results after osteochondral transplantation in the knee joint: a report on 35 cases. In: Program and abstracts of the 67th annual meeting of the American Academy of Orthopaedic Surgeons; March 15-19, 2000; Orlando, Fla. Paper No. 127.
  4. Rumi MN, Buhl KM, Frauenhoffer EE, DeMarco C, Donahue HJ, Black KP. Intermittent high intensity loading exercise damages articular cartilage in the knees of young rats. In: Program and abstracts of the 67th annual meeting of the American Academy of Orthopaedic Surgeons; March 15-19, 2000; Orlando, Fla. Paper No. 130.
  5. Wyland DJ, Guilak F, Elliott DM, Setton LA, Vail TP. Degeneration of articular cartilage after meniscal incision or partial meniscectomy. In: Program and abstracts of the 67th annual meeting of the American Academy of Orthopaedic Surgeons; March 15-19, 2000; Orlando, Fla. Paper No. 132.

Suggested Readings

  • Bobic V. Arthroscopic osteochondral autograft transplantation in anterior cruciate ligament reconstruction: a preliminary clinical study. Knee Surg Sports Traumatol Arthroscopy. 1966;3:262-264.
  • Brittberg M, Lindahl A, Nilsson A, Ohlson 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.
  • Curl WW, Krome J, Gordon ES, Rushing J, Smith BP, Poehling GG. Cartilage injuries: a review of 31,516 knee arthroscopies. Arthroscopy. 1997;13:456-460.
  • Dew T L, Martin R A. Functional, radiographic and histological assessment of healing of autogenous osteochondral grafts and full-thickness cartilage defects in the talus of dogs. Am J Vet Res. 1992;53:2141-2152.
  • Duchow J, Hess, T, Kohn, D. Primary stability of press-fit-implanted osteochondral grafts. Influence of graft size, repeated insertion and harvesting technique. Am J Sports Med. 2000;28:24-27.
  • Grande DA, Pitman MI Peterson L, et al.The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. J Orthop Res. 1989;7:208-218.
  • Hangody L, Kish G, Kárpáti Z, Szerb I, Udvarhelyi I. Arthroscopic Autogenous osteochondral mosaicplasty for the treatment of femoral condylar articular defects. Knee Surg Sports Traumatol, Arthroscopy. 19975;5:262-267.
  • Itay S, Abramovici A, Yosipovitch Z, et al. Correction of defects in articular cartilage by implants of cultured embryogenic chondrocytes. Trans Orthop Res Soc. 1988;13:112.
  • Lane J M, Brighton C T, Ottens H R, Lipton M.Joint resurfacing in the rabbit using an autologous osteochondral graft. A biochemical and metabolic study of cartilage viability J Bone Joint Surg. 1977;59-A:218-222.
  • Mandelbaum BR, Browne JE, Fu F, et al.Articular cartilage lesions of the knee. Am J Sports Med. 1998;26:853-861.
  • Mankin HJ. Chondrocyte transplantation - one answer to an old question.N Engl J Med. 1994;331:940-941.
  • Matsusue Y, Yamamuro T, Hama H. Case report: arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption. Arthroscopy. 1993;9:318-321.
  • Miniaci A, Evans P, Hurtig M: Proceedings of the 17th AANA annual meeting, Orlando, Fla, 1998.
  • Müller W. Osteochondrosis dissecans. In: Progress in Orthopaedic Surgery. Hastings, Del: Springer; 1978;3:135.
  • Outerbridge HK, Outerbridge AR, Outerbridge RE. The use of a lateral patellar autologous graft for the repair of a large osteochondral defet in the knee. J Bone Joint Surg. 1995;77-A:65-A72.
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  • Simonian PT, Sussmann PS, Wickiewicz TL, Paletta GA, Warren RF. Contact pressures at osteochondral donor sites in the knee. Am J Sports Med. 1998;26:491-494.
  • Wilson WJ, Jacobs JE. Patellar graft for severely depressed comminuted fractures of the lateral tibial condyle. J Bone Joint Surg. 1952;34-A:436-442.
  • Yamashita F, Sakakida K, Suzu F, Takai S. The transplantation of an autogenic osteochondral fragment for osteochondritis dissecans of the knee. Clin Orthop. 1985;201:43-50.