Clinical Applicability of Autologous Chondrocyte Implantation for the
Treatment of Osteochondral Defects: A Meta-analysis

Faisal   I.   Almohaileb; Zafar      Rasheed

doi:10.2174/0115733971249660231101102757

Abstract

Purpose: Osteoarthritis and other joint disorders are the leading cause of disability in the elderly and the treatment of joint lesions is challenging. Autologous chondrocyte implantation (ACI) has been reported with variable effects for the treatment of osteochondral and other joint lesions. In this study, we performed a meta-analysis of the recent literature to determine the clinical applicability of ACI for osteochondral defects.

Methods: A meta-analysis was performed on the recent literature showing the effects of ACI on osteochondral defects. The PUBMED, ScienceDirect and Google Scholar databases were used to identify eligible studies from Jan 2010 to Sep 2022. Both fixed and random models of meta-analysis were applied with all reported scoring systems to quantify the effectiveness of ACI on osteochondral defects.

Results: The pool data of 965 patients as a case series after ACI from a fixed model showed a significant improvement in the osteochondral defects (odds ratio = 8.75, 95%CI = 7.127 to 10.743, p = 0.000). These results were further verified by a random model of meta-analysis. The data also showed a substantial heterogeneity among the studies used in the meta-analysis (Q-value = 160.41, I-squared = 87.53, p = 0.000). Furthermore, this meta-analysis also compared different ACI procedures with different scoring systems but the overall outcome remains the same as ACI was found to be useful for the healing of the osteochondral defects.

Conclusion: This meta-analysis of 965 case series revealed that the ACI markedly improved the damage osteochondral defects scores but the optimal treatment is still controversial, therefore further studies are needed to validate these findings in a clinical setting.

Keywords: Meta-analysis, ACI, osteochondral defects, AOFAS, damage joint scores, osteoarthritis.

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[1]
D’Ambrosi R, Maccario C, Serra N, Liuni F, Usuelli FG. Osteochondral lesions of the talus and autologous matrix-induced chondrogenesis: Is age a negative predictor outcome? Arthroscopy  2017; 33(2): 428-35.
 [http://dx.doi.org/10.1016/j.arthro.2016.09.030] [PMID: 27956234]

[2]
Colombini A, Libonati F, Lopa S, Peretti GM, Moretti M, de Girolamo L. Autologous chondrocyte implantation provides good long-term clinical results in the treatment of knee osteoarthritis: A systematic review. Knee Surg Sports Traumatol Arthrosc  2022; 31(6): 2338-48.
 [http://dx.doi.org/10.1007/s00167-022-07030-2] [PMID: 35716187]

[3]
Barié A, Kruck P, Sorbi R, et al. Prospective long-term follow-up of autologous chondrocyte implantation with periosteum versus matrix-associated autologous chondrocyte implantation: A randomized clinical trial. Am J Sports Med  2020; 48(9): 2230-41.
 [http://dx.doi.org/10.1177/0363546520928337] [PMID: 32667270]

[4]
Migliorini F, Eschweiler J, Goetze C, et al. Cell therapies for chondral defects of the talus: A systematic review. J Orthop Surg Res  2022; 17(1): 308.
 [http://dx.doi.org/10.1186/s13018-022-03203-4] [PMID: 35690865]

[5]
Heiss R, Guermazi A, Janka R, et al. Update: Posttreatment imaging of the knee after cartilage repair. Semin Musculoskelet Radiol  2022; 26(3): 216-29.
 [http://dx.doi.org/10.1055/s-0042-1743405] [PMID: 35654091]

[6]
Niethammer TR, Gallik D, Chevalier Y, et al. Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint. Int Orthop  2021; 45(6): 1483-91.
 [http://dx.doi.org/10.1007/s00264-020-04884-4] [PMID: 33280063]

[7]
Niemeyer P, Laute V, Zinser W, et al. Clinical outcome and success rates of ACI for cartilage defects of the patella: A subgroup analysis from a controlled randomized clinical phase II trial (CODIS study). Arch Orthop Trauma Surg  2020; 140(6): 717-25.
 [http://dx.doi.org/10.1007/s00402-019-03264-x] [PMID: 31451902]

[8]
Welsch GH, Mamisch TC, Quirbach S, Zak L, Marlovits S, Trattnig S. Evaluation and comparison of cartilage repair tissue of the patella and medial femoral condyle by using morphological MRI and biochemical zonal T2 mapping. Eur Radiol  2009; 19(5): 1253-62.
 [http://dx.doi.org/10.1007/s00330-008-1249-6] [PMID: 19104822]

[9]
Niemeyer P, Andereya S, Angele P, et al. Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU). Z Orthop Unfall  2013; 151(1): 38-47.
 [http://dx.doi.org/10.1055/s-0032-1328207]

[10]
Oussedik S, Tsitskaris K, Parker D. Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: A systematic review. Arthroscopy  2015; 31(4): 732-44.
 [http://dx.doi.org/10.1016/j.arthro.2014.11.023] [PMID: 25660008]

[11]
Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Südkamp NP, Niemeyer P. Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med  2012; 40(1): 58-67.
 [http://dx.doi.org/10.1177/0363546511423522] [PMID: 21969180]

[12]
Richter DL, Schenck RC Jr, Wascher DC, Treme G. Knee articular cartilage repair and restoration techniques. Sports Health  2016; 8(2): 153-60.
 [http://dx.doi.org/10.1177/1941738115611350] [PMID: 26502188]

[13]
Minas T, Ogura T, Bryant T. Autologous chondrocyte implantation. JBJS Essential Surg Tech  2016; 6(2): e24.
 [http://dx.doi.org/10.2106/JBJS.ST.16.00018] [PMID: 30237933]

[14]
Minas T, Gomoll AH, Solhpour S, Rosenberger R, Probst C, Bryant T. Autologous chondrocyte implantation for joint preservation in patients with early osteoarthritis. Clin Orthop Relat Res  2010; 468(1): 147-57.
 [http://dx.doi.org/10.1007/s11999-009-0998-0] [PMID: 19653049]

[15]
Pareek A, Carey JL, Reardon PJ, Peterson L, Stuart MJ, Krych AJ. Long-term outcomes after autologous chondrocyte implantation. Cartilage  2016; 7(4): 298-308.
 [http://dx.doi.org/10.1177/1947603516630786] [PMID: 27688838]

[16]
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ  2021; 372(71): n71.
 [http://dx.doi.org/10.1136/bmj.n71] [PMID: 33782057]

[17]
Critical Appraisal Skills Programme (CASP) 2019 (Systematic Review) Checklist. 2019. Available from:https://casp-uk.net/casp-tools-checklists/ (Accessed: March 16, 2022) 

[18]
Ioannidis JPA. Interpretation of tests of heterogeneity and bias in meta-analysis. J Eval Clin Pract  2008; 14(5): 951-7.
 [http://dx.doi.org/10.1111/j.1365-2753.2008.00986.x] [PMID: 19018930]

[19]
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ  2003; 327(7414): 557-60.
 [http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]

[20]
Sterne JAC, Egger M. Funnel plots for detecting bias in meta-analysis. J Clin Epidemiol  2001; 54(10): 1046-55.
 [http://dx.doi.org/10.1016/S0895-4356(01)00377-8] [PMID: 11576817]

[21]
Deliwala U, Sethia SJ. Gel-based autologous chondrocyte implantation in a patient with noncontained osteochondral knee defect at 9-year follow-up. Case Rep Orthop  2022; 2022: 1-6.
 [http://dx.doi.org/10.1155/2022/6946860] [PMID: 35615459]

[22]
Zorzi AR, Antonioli E, Kaleka CC, et al. Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: The Hospital Israelita Albert Einstein experience. Einstein  2022; 20: eAO6819.
 [http://dx.doi.org/10.31744/einstein_journal/2022AO6819] [PMID: 35544896]

[23]
Niemeyer P, Hanus M, Belickas J, et al. Treatment of large cartilage defects in the knee by hydrogel-based autologous chondrocyte implantation: Two-year results of a prospective, multicenter, single-arm phase III trial. Cartilage  2022; 13(1)
 [http://dx.doi.org/10.1177/19476035221085146] [PMID: 35354310]

[24]
Niethammer TR, Uhlemann F, Zhang A, Holzgruber M, Wagner F, Müller PE. Hydrogel-based autologous chondrocyte implantation leads to subjective improvement levels comparable to scaffold based autologous chondrocyte implantation. Knee Surg Sports Traumatol Arthrosc  2022; 30(10): 3386-92.
 [http://dx.doi.org/10.1007/s00167-022-06886-8] [PMID: 35226109]

[25]
Hoburg A, Niemeyer P, Laute V, et al. Safety and efficacy of matrix-associated autologous chondrocyte implantation with spheroids for patellofemoral or tibiofemoral defects: A 5-year follow-up of a phase 2, dose-confirmation trial. Orthop J Sports Med  2022; 10(1)
 [http://dx.doi.org/10.1177/23259671211053380] [PMID: 35071653]

[26]
Li X, Li S, Qian J, Chen Y, Zhou Y, Fu P. Early efficacy of type I collagen-based matrix-assisted autologous chondrocyte transplantation for the treatment of articular cartilage lesions. Front Bioeng Biotechnol  2021; 9: 760179.
 [http://dx.doi.org/10.3389/fbioe.2021.760179] [PMID: 34778233]

[27]
Lenz CG, Tan S, Carey AL, Ang K, Schneider T. Matrix-Induced Autologous Chondrocyte Implantation (MACI) grafting for osteochondral lesions of the talus. Foot Ankle Int  2020; 41(9): 1099-105.
 [http://dx.doi.org/10.1177/1071100720935110] [PMID: 32639169]

[28]
López-Alcorocho JM, Guillén-Vicente I, Rodríguez-Iñigo E, et al. High-density autologous chondrocyte implantation as treatment for ankle osteochondral defects. Cartilage  2021; 12(3): 307-19.
 [http://dx.doi.org/10.1177/1947603519835898] [PMID: 30880428]

[29]
Kreulen C, Giza E, Walton J, Sullivan M. Seven-year follow-up of matrix-induced autologous implantation in talus articular defects. Foot Ankle Spec  2018; 11(2): 133-7.
 [http://dx.doi.org/10.1177/1938640017713614] [PMID: 28587484]

[30]
Pagliazzi G, Vannini F, Battaglia M, Ramponi L, Buda R. Autologous chondrocyte implantation for talar osteochondral lesions: Comparison between 5-year follow-up magnetic resonance imaging findings and 7-year follow-up clinical results. J Foot Ankle Surg  2018; 57(2): 221-5.
 [http://dx.doi.org/10.1053/j.jfas.2017.05.013] [PMID: 29146220]

[31]
Desando G, Bartolotti I, Vannini F, et al. Repair potential of matrix-induced bone marrow aspirate concentrate and matrix-induced autologous chondrocyte implantation for talar osteochondral repair. Cartilage  2017; 8(1): 50-60.
 [http://dx.doi.org/10.1177/1947603516642573] [PMID: 27994720]

[32]
Buda R, Vannini F, Castagnini F, et al. Regenerative treatment in osteochondral lesions of the talus: Autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation. Int Orthop  2015; 39(5): 893-900.
 [http://dx.doi.org/10.1007/s00264-015-2685-y] [PMID: 25662594]

[33]
Kwak SK, Kern BS, Ferkel RD, Chan KW, Kasraeian S, Applegate GR. Autologous chondrocyte implantation of the ankle: 2- to 10-year results. Am J Sports Med  2014; 42(9): 2156-64.
 [http://dx.doi.org/10.1177/0363546514540587] [PMID: 25056988]

[34]
Lee KT, Kim JS, Young KW, et al. The use of fibrin matrix-mixed gel-type autologous chondrocyte implantation in the treatment for osteochondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc  2013; 21(6): 1251-60.
 [http://dx.doi.org/10.1007/s00167-012-2096-1] [PMID: 22752415]

[35]
Battaglia M, Vannini F, Buda R, et al. Arthroscopic autologous chondrocyte implantation in osteochondral lesions of the talus: Mid-term T2-mapping MRI evaluation. Knee Surg Sports Traumatol Arthrosc  2011; 19(8): 1376-84.
 [http://dx.doi.org/10.1007/s00167-011-1509-x] [PMID: 21503808]

[36]
Giza E, Sullivan M, Ocel D, et al. Matrix-induced autologous chondrocyte implantation of talus articular defects. Foot Ankle Int  2010; 31(9): 747-53.
 [http://dx.doi.org/10.3113/FAI.2010.0747] [PMID: 20880476]

[37]
Kraeutler MJ, Aliberti GM, Scillia AJ, McCarty EC, Mulcahey MK. Microfracture versus drilling of articular cartilage defects: A systematic review of the basic science evidence. Orthop J Sports Med  2020; 8(8)
 [http://dx.doi.org/10.1177/2325967120945313] [PMID: 32913875]

[38]
Frisbie DD, Trotter GW, Powers BE, et al. Arthroscopic subchondral bone plate microfracture technique augments healing of large chondral defects in the radial carpal bone and medial femoral condyle of horses. Vet Surg  1999; 28(4): 242-55.
 [http://dx.doi.org/10.1053/jvet.1999.0242] [PMID: 10424704]

[39]
Bekkers JEJ, Inklaar M, Saris DBF. Treatment selection in articular cartilage lesions of the knee: A systematic review. Am J Sports Med  2009; 37(1_suppl): 148-55.
 [http://dx.doi.org/10.1177/0363546509351143] [PMID: 19934442]

[40]
Lim HC, Bae JH, Song SH, Park YE, Kim SJ. Current treatments of isolated articular cartilage lesions of the knee achieve similar outcomes. Clin Orthop Relat Res  2012; 470(8): 2261-7.
 [http://dx.doi.org/10.1007/s11999-012-2304-9] [PMID: 22422593]

[41]
Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: An evidence-based systematic analysis. Am J Sports Med  2009; 37(10): 2053-63.
 [http://dx.doi.org/10.1177/0363546508328414] [PMID: 19251676]

[42]
Gobbi A, Karnatzikos G, Kumar A. Long-term results after microfracture treatment for full-thickness knee chondral lesions in athletes. Knee Surg Sports Traumatol Arthrosc  2014; 22(9): 1986-96.
 [http://dx.doi.org/10.1007/s00167-013-2676-8] [PMID: 24051505]

[43]
Goyal D, Keyhani S, Lee EH, Hui JHP. Evidence-based status of microfracture technique: A systematic review of level I and II studies. Arthroscopy  2013; 29(9): 1579-88.
 [http://dx.doi.org/10.1016/j.arthro.2013.05.027] [PMID: 23992991]

[44]
Von Keudell A, Atzwanger J, Forstner R, Resch H, Hoffelner T, Mayer M. Radiological evaluation of cartilage after microfracture treatment: A long-term follow-up study. Eur J Radiol  2012; 81(7): 1618-24.
 [http://dx.doi.org/10.1016/j.ejrad.2011.04.071] [PMID: 21684098]

[45]
Bert JM. Abandoning microfracture of the knee: Has the time come? Arthroscopy  2015; 31(3): 501-5.
 [http://dx.doi.org/10.1016/j.arthro.2014.12.018] [PMID: 25744322]

[46]
Johnson LL, Spector M. The New Microfracture: All Things Considered. Arthroscopy  2015; 31(6): 1028-31.
 [http://dx.doi.org/10.1016/j.arthro.2015.04.073] [PMID: 26048762]

[47]
Minas T, Nehrer S. Current concepts in the treatment of articular cartilage defects. Orthopedics  1997; 20(6): 525-38.
 [http://dx.doi.org/10.3928/0147-7447-19970601-08] [PMID: 9195635]

[48]
Gillogly SD, Voight M, Blackburn T. Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation. J Orthop Sports Phys Ther  1998; 28(4): 241-51.
 [http://dx.doi.org/10.2519/jospt.1998.28.4.241] [PMID: 9785259]

[49]
Tran TM, Sosa B, O’Connell A, Chu T, Cottrell JA, Chang SL. A meta-analysis of non-osteoarthritis and osteoarthritis chondrocyte gene expression to determine the efficacy of autologous chondrocyte transplantation as a viable treatment option. Med Case Rep Short Rev  2019; 2(1): 264.
 [PMID: 34970658]

[50]
Schneider TE, Karaikudi S. Matrix-Induced Autologous Chondrocyte Implantation (MACI) grafting for osteochondral lesions of the talus. Foot Ankle Int  2009; 30(9): 810-4.
 [http://dx.doi.org/10.3113/FAI.2009.0810] [PMID: 19755063]

[51]
Whittaker JP, Smith G, Makwana N, et al. Early results of autologous chondrocyte implantation in the talus. J Bone Joint Surg Br  2005; 87-B(2): 179-83.
 [http://dx.doi.org/10.1302/0301-620X.87B2.15376] [PMID: 15736739]

[52]
Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation – a systematic review. Osteoarthritis Cartilage  2011; 19(7): 779-91.
 [http://dx.doi.org/10.1016/j.joca.2011.02.010] [PMID: 21333744]

[53]
FDA approves first autologous cellularized scaffold for the repair of cartilage defects of the knee.  Available from:https://www.fda.gov/news-events/press-announcements/fda-approves-first-autologous-cellularized-scaffold-repair-cartilage-defects-knee (Accessed on 20/6/2023) 

[54]
Wood JJ, Malek MA, Frassica FJ, et al. Autologous cultured chondrocytes: Adverse events reported to the United States Food and Drug Administration. J Bone Joint Surg Am  2006; 88(3): 503-7.
 [http://dx.doi.org/10.2106/00004623-200603000-00006] [PMID: 16510814]

[55]
Niemeyer P, Pestka JM, Kreuz PC, et al. Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med  2008; 36(11): 2091-9.
 [http://dx.doi.org/10.1177/0363546508322131] [PMID: 18801942]

[56]
Procedure for early osteoarthritis to reduce need for knee replacement.  Available from:versusarthritis.org/research/research-achievements/new-procedure-for-early-osteoarthritis/#:~:text=symptoms%20and%20treatments.,What%20is%20Autologous%20Chondrocyte%20Implantation%3F,cartilage%20cells%20in%20a%20laboratory">https://www.versusarthritis.org/research/research-achievements/new-procedure-for-early-osteoarthritis/#:~:text=symptoms%20and%20treatments.,What%20is%20Autologous%20Chondrocyte%20Implantation%3F,cartilage%20cells%20in%20a%20laboratory (Accessed 02/02/2023)

[57]
Shen H, He Y, Wang N, et al. Enhancing the potential of aged human articular chondrocytes for high-quality cartilage regeneration. FASEB J  2021; 35(3): e21410.
 [http://dx.doi.org/10.1096/fj.202002386R] [PMID: 33617078]

[58]
Autologous chondrocyte implantation for treating symptomatic articular cartilage defects of the knee.  Available from:https://www.nice.org.uk/guidance/TA477/chapter/1-Recommendations (Accessed 02/02/2023)

[59]
Roberts S, McCall IW, Darby AJ, et al. Autologous chondrocyte implantation for cartilage repair: Monitoring its success by magnetic resonance imaging and histology. Arthritis Res  2003; 5(1): R60-73.
 [http://dx.doi.org/10.1186/ar613] [PMID: 12716454]

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DOI https://dx.doi.org/10.2174/0115733971249660231101102757	Print ISSN 1573-3971
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