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Meta-Analysis
. 2010 Oct 6;2010(10):CD003323.
doi: 10.1002/14651858.CD003323.pub3.

Autologous chondrocyte implantation for full thickness articular cartilage defects of the knee

Haris S Vasiliadis  1 , Jason Wasiak
Affiliations
Meta-Analysis

Autologous chondrocyte implantation for full thickness articular cartilage defects of the knee

Haris S Vasiliadis et al. Cochrane Database Syst Rev. .

Abstract

Background: Treatments for managing articular cartilage defects of the knee, including drilling and abrasion arthroplasty, are not always effective. When they are, long-term benefits may not be maintained and osteoarthritis may develop. An alternative is autologous chondrocyte implantation (ACI), the surgical implantation of healthy cartilage cells into the damaged areas.

Objectives: To determine the efficacy and safety of ACI in people with full thickness articular cartilage defects of the knee.

Search strategy: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (3 December 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE (1950 to November Week 3 2008), EMBASE (1980 to Week 48 2008), SPORTDiscus (3 December 2008), the WHO International Clinical Trials Registry Platform (4 December 2008), and Current Controlled Trials (3 December 2008).

Selection criteria: Randomised and quasi-randomised trials comparing ACI with any other type of treatment (including no treatment or placebo) for symptomatic cartilage defects of the medial or lateral femoral condyle, femoral trochlea or patella.

Data collection and analysis: Review authors selected studies for inclusion independently. We assessed risk of bias based on adequacy of the randomisation and allocation concealment process, potential for selection bias after allocation and level of masking. We did not pool data due to clinical and methodological heterogeneity.

Main results: Six heterogeneous trials were identified with 431 participants. Methodological flaws of the included trials included incomplete follow-up and inadequate reporting of outcomes. Three trials compared ACI versus mosaicplasty. One reported statistically significant results in favour of ACI at one year in the numbers of people with 'good' or 'excellent' functional results. Conversely, another trial found significant improvement for the mosaicplasty group when assessed using one functional scoring system at two years, but no statistically significant differences based on two other scoring systems. A third trial found no difference between ACI and mosaicplasty, 10 months on average after the surgery.There was no statistically significant difference in functional outcomes at two years in single trials comparing ACI with microfracture or characterised chondrocyte implantation versus microfracture. The results of the sixth trial comparing matrix-guided ACI versus microfracture were undermined by the severe loss to follow-up.

Authors' conclusions: There is insufficient evidence to draw conclusions on the use of ACI for treating full thickness articular cartilage defects in the knee. Further good quality randomised controlled trials with long-term functional outcomes are required.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Forest plot of comparison: 1 ACI versus mosaicplasty, outcome: 1.7 Satisfactory outcome (various criteria) ‐ exploratory analysis.
1.1
1.1. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 1 Good or excellent functional results (modified Cincinatti rating system).
1.2
1.2. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 2 Arthroscopic assessment at one year (ICRS grade 1 or 2).
1.3
1.3. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 3 Lysholm scores (0: worst to 100: best).
1.4
1.4. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 4 Tegner scores (0: worst to 10: best) at 24 months.
1.5
1.5. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 5 Meyers scores (higher scores better) at 24 months.
1.6
1.6. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 6 Excellent outcome (various definitions).
1.7
1.7. Analysis
Comparison 1 ACI versus mosaicplasty, Outcome 7 Satisfactory outcome (various criteria) ‐ exploratory analysis.
2.1
2.1. Analysis
Comparison 2 ACI versus microfracture, Outcome 1 Presence of hyaline cartilage in biopsy.
2.2
2.2. Analysis
Comparison 2 ACI versus microfracture, Outcome 2 Failure and further procedures.
3.1
3.1. Analysis
Comparison 3 MACI versus microfracture, Outcome 1 Lysholm scores (0: worst to 100: best).
3.2
3.2. Analysis
Comparison 3 MACI versus microfracture, Outcome 2 Tegner scores (0: worst to 10: best) at 24 months.
3.3
3.3. Analysis
Comparison 3 MACI versus microfracture, Outcome 3 ICRS patient score (grade 1 or 2) at 24 months.
4.1
4.1. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 1 Knee function up to 18 months (KOOS ("overall" minus 'sport' domain): 0: extreme knee problems, 100: no knee problems).
4.2
4.2. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 2 KOOS (improvement from baseline at 36 months).
4.3
4.3. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 3 KOOS improvement from baseline at 36 months (adjusted data).
4.4
4.4. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 4 Treatment failure requiring re‐intervention (up to 36 months).
4.5
4.5. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 5 Adverse events (at 18 months).
4.6
4.6. Analysis
Comparison 4 CCI (characterised chrondrocyte implantation) versus microfracture, Outcome 6 Adverse events (at 36 months).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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    1. Saris DB, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, et al. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. American Journal of Sports Medicine 2009;37 Suppl 1:10S‐19S. [PUBMED: 19846694] - PubMed
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    1. Assche D, Staes F, Caspel D, Vanlauwe J, Bellemans J, Saris DB, et al. Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2‐year follow‐up. Knee Surgery, Sports Traumatology, Arthroscopy 2010;18(4):486‐95. - PubMed

References to studies excluded from this review

Anderson 2003 {published data only}
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Bartlett 2005 {published data only}
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    1. Bartlett W, Skinner JA, Gooding CR, Carrington RW, Flanagan AM, Briggs TW, et al. Autologous chondrocyte implantation versus matrix‐induced autologous chondrocyte implantation for osteochondral defects of the knee: a prospective randomised study. Journal of Bone and Joint Surgery ‐ British Volume 2005;87(5):640‐5. [PUBMED: 15855365] - PubMed
Behrens 2006 {published data only}
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Bickerstaff {published data only}
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Brittberg {published data only}
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Ebert 2008 {published data only}
    1. Ebert JR, Robertson WB, Lloyd DG, Zheng MH, Wood DJ, Ackland T. Traditional vs accelerated approaches to post‐operative rehabilitation following matrix‐induced autologous chondrocyte implantation (MACI): comparison of clinical, biomechanical and radiographic outcomes. Osteoarthritis & Cartilage 2008;16(10):1131‐40. [PUBMED: 18434214] - PubMed
Gooding 2006 {published data only}
    1. Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flanagan A. A prospective, randomised study comparing two techniques of autologous chondrocyte implantation for osteochondral defects in the knee: Periosteum covered versus type I/III collagen covered. Knee 2006;13(3):203‐10. [PUBMED: 16644224] - PubMed
Gudas 2005 {published data only}
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Jacobsen {published data only}
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Joergensen {published data only}
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Keating {published data only}
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Kon 2009 {published data only}
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Park 2008 {published data only}
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Schneider 2003 {published data only}
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Trial 1 {published data only}
    1. Identified in Jobanputra P, Parry D, Fry‐Smith A, Burls A. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review. Table 3 RCTs currently in progress. Health Technology Assessment 2001; Vol. 5, issue 11:11. Available from: www.ncchta.org/fullmono/mon511.pdf. - PubMed
Trial 2 {published data only}
    1. Identified in Jobanputra P, Parry D, Fry‐Smith A, Burls A. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review. Table 3 RCTs currently in progress. Health Technology Assessment 2001; Vol. 5, issue 11:11. Available from: http://www.ncchta.org/fullmono/mon511.pdf. - PubMed
Trial 3 {published data only}
    1. Identified in Jobanputra P, Parry D, Fry‐Smith A, Burls A. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review. Table 3 RCTs currently in progress. Health Technology Assessment [serial on the Internet] 2001; Vol. 5, issue 11:11. Available from: http://www.ncchta.org/fullmono/mon511.pdf. - PubMed
Trial 4 {published data only}
    1. Identified in Jobanputra P, Parry D, Fry‐Smith A, Burls A. Effectiveness of autologous chondrocyte transplantation for hyaline cartilage defects in knees: a rapid and systematic review. Table 3 RCTs currently in progress. Health Technology Assessment 2001; Vol. 5, issue 11:11. Available from: http://www.ncchta.org/fullmono/mon511.pdf. - PubMed
Visna 2004 {published data only}
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Wondrasch 2009 {published data only}
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Zeifang 2010 {published data only}
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References to ongoing studies

ACTIVE {unpublished data only}
    1. Ali MS. ACTIVE: Cartilage repair by autologous chondrocyte transplantation vs existing conventional treatments. National Research Register (NRR) Archive. https://portal.nihr.ac.uk/Profiles/NRR.aspx?Publication_ID=N0557164195 (accessed 03 July 2009). [N0557164195]
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Barnouin {unpublished data only}
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Crawford {published and unpublished data}
    1. Confirmatory study of NeoCart in knee cartilage repair. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01066702 (accessed 31 May 2010).
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Dubrana {unpublished data only}
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Fickert {unpublished data only}
    1. Fickert S. Efficacy and safety study of co.don chondrosphere to treat cartilage defects. Available from: http://clinicaltrials.gov/show/NCT01222559 (accessed 17 February 2011).
Richardson {unpublished data only}
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Roth‐Ben Arie {published and unpublished data}
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    1. Roth‐Ben Arie Z. Comparison of BioCartII with microfracture for treatment of cartilage defects of the femoral condyle. http://www.clinicaltrials.gov/ct2/show/NCT00729716 (accessed 17 February 2010).
SUMMIT {unpublished data only}
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References to other published versions of this review

Vasiliadis 2010
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