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In vitro cell quality of articular chondrocytes assigned for autologous implantation in dependence of specific patient characteristics

  • Orthopaedic Surgery
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Objective

Autologous chondrocyte implantation (ACI) is a well-established therapeutic option for the treatment of cartilage defects of the knee joint. Since information concerning the cellular aspects of ACI is still limited, the aim of the present study was to investigate relevant differences between chondrocyte quality after in vitro cultivation and possible correlations with patient-specific factors.

Design

Cell quality of 252 consecutive ACI patients was assessed after chondrocyte in vitro expansion by determination of the expression of cartilage relevant surface marker CD44 and cartilage-specific differentiation markers (aggrecan and collagen type II). All cell quality parameters were correlated with patient-specific parameters, such as age, size and defect location, number of defects and grade of joint degeneration according to the Kellgren–Lawrence classification.

Results

Neither the expression of CD44, aggrecan or collagen type II nor cell density or viability after proliferation seemed to correlate with the grade of joint degeneration, defect aetiology or patient gender. However, chondrocytes harvested from the knee joints of patients at less than 20 years of age showed significantly higher expression rates of cartilage-specific markers when compared to older patients’ chondrocytes.

Conclusions

The present study identifies relevant differences concerning chondrocyte quality after in vitro expansion in a highly preselected study population of 252 patients that from a surgical point of view were eligible for ACI. With the exception of patients aged 20 years or younger, no patient-specific parameters could be identified which might allow anticipation of cell quality in individual patients.

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References

  1. Erggelet C, Sittinger M, Lahm A (2003) The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy 19:108–110

    Article  PubMed  Google Scholar 

  2. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895

    Article  PubMed  CAS  Google Scholar 

  3. Bentley G, Biant LC, Carrington RW, Akmal M, Goldberg A, Williams AM, Skinner JA, Pringle J (2003) A prospective, randomised comparison of autologous chondrocyte implantation versus mosaicplasty for osteochondral defects in the knee. J Bone Jt Surg Br 85:223–230

    Article  CAS  Google Scholar 

  4. Jones DG, Peterson L (2006) Autologous chondrocyte implantation. J Bone Jt Surg Am 88:2502–2520

    Google Scholar 

  5. Niemeyer P, Pestka JM, Kreuz PC, Erggelet C, Schmal H, Suedkamp NP, Steinwachs M (2008) Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint. Am J Sports Med 36:2091–2099

    Article  PubMed  Google Scholar 

  6. Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flanagan A (2006) 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 13:203–210

    Article  PubMed  CAS  Google Scholar 

  7. Friemert B, Oberlander Y, Danz B, Haberle HJ, Bahren W, Gerngross H, Schwarz W (2002) MRI vs. arthroscopy in the diagnosis of cartilage lesions in the knee. Can MRI take place of arthroscopy? Zentralbl Chir 127:822–827

    Article  PubMed  CAS  Google Scholar 

  8. Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ (2008) Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol 22:351–384

    Article  PubMed  CAS  Google Scholar 

  9. Buschmann MD, Gluzband YA, Grodzinsky AJ, Kimura JH, Hunziker EB (1992) Chondrocytes in agarose culture synthesize a mechanically functional extracellular matrix. J Orthop Res 10:745–758

    Article  PubMed  CAS  Google Scholar 

  10. Bajorath J (2000) Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions. Proteins 39:103–111

    Article  PubMed  CAS  Google Scholar 

  11. Albrecht C, Schlegel W, Eckl P, Jagersberger T, Sadeghi K, Berger A, Vecsei V, Marlovits S (2009) Alterations in CD44 isoforms and HAS expression in human articular chondrocytes during the de- and re-differentiation processes. Int J Mol Med 23:253–259

    PubMed  CAS  Google Scholar 

  12. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313

    Article  PubMed  CAS  Google Scholar 

  13. Rousche KT, Knudson CB (2002) Temporal expression of CD44 during embryonic chick limb development and modulation of its expression with retinoic acid. Matrix Biol 21:53–62

    Article  PubMed  CAS  Google Scholar 

  14. Behrens P, Bosch U, Bruns J, Erggelet C, Esenwein SA, Gaissmaier C, Krackhardt T, Lohnert J, Marlovits S, Meenen NM, Mollenhauer J, Nehrer S, Niethard FU, Noth U, Perka C, Richter W, Schafer D, Schneider U, Steinwachs M, Weise K (2004) Indications and implementation of recommendations of the working group “Tissue Regeneration and Tissue Substitutes” for autologous chondrocyte transplantation (ACT). Z Orthop Ihre Grenzgeb 142:529–539

    Article  PubMed  CAS  Google Scholar 

  15. Cole BJ, Pascual-Garrido C, Grumet RC (2009) Surgical management of articular cartilage defects in the knee. J Bone Jt Surg Am 91:1778–1790

    Google Scholar 

  16. Niemeyer P, Pestka JM, Kreuz PC, Salzmann GM, Kostler W, Sudkamp NP, Steinwachs M (2010) Standardized cartilage biopsies from the intercondylar notch for autologous chondrocyte implantation (ACI). Knee Surg Sports Traumatol Arthrosc 18:1122–1127

    Article  PubMed  Google Scholar 

  17. Hauselmann HJ, Fernandes RJ, Mok SS, Schmid TM, Block JA, Aydelotte MB, Kuettner KE, Thonar EJ (1994) Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads. J Cell Sci 107(Pt 1):17–27

    PubMed  Google Scholar 

  18. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502

    Article  PubMed  CAS  Google Scholar 

  19. Burdi AR (1965) Toluidine blue-Alizarin red S staining of cartilage and bone in whole-mount skeletons in vitro. Stain Technol 40:45–48

    PubMed  CAS  Google Scholar 

  20. Camplejohn KL, Allard SA (1988) Limitations of safranin ‘O’ staining in proteoglycan-depleted cartilage demonstrated with monoclonal antibodies. Histochemistry 89:185–188

    Article  PubMed  CAS  Google Scholar 

  21. Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP (2008) Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 36:235–246

    Article  PubMed  Google Scholar 

  22. Levine DW, Roaf PL, Duguay SJ (2009) Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 37:e3 (author reply e4)

    Google Scholar 

  23. Pietschmann MF, Horng A, Niethammer T, Pagenstert I, Sievers B, Jansson V, Glaser C, Muller PE (2009) Cell quality affects clinical outcome after MACI procedure for cartilage injury of the knee. Knee Surg Sports Traumatol Arthrosc 17:1305–1311

    Article  PubMed  Google Scholar 

  24. Grogan SP, Barbero A, Diaz-Romero J, Cleton-Jansen AM, Soeder S, Whiteside R, Hogendoorn PC, Farhadi J, Aigner T, Martin I, Mainil-Varlet P (2007) Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity. Arthritis Rheum 56:586–595

    Article  PubMed  Google Scholar 

  25. Chubinskaya S, Kumar B, Merrihew C, Heretis K, Rueger DC, Kuettner KE (2002) Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1). Biochim Biophys Acta 1588:126–134

    PubMed  CAS  Google Scholar 

  26. Hollander AP, Pidoux I, Reiner A, Rorabeck C, Bourne R, Poole AR (1995) Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J Clin Invest 96:2859–2869

    Article  PubMed  CAS  Google Scholar 

  27. Iqbal J, Dudhia J, Bird JL, Bayliss MT (2000) Age-related effects of TGF-beta on proteoglycan synthesis in equine articular cartilage. Biochem Biophys Res Commun 274:467–471

    Article  PubMed  CAS  Google Scholar 

  28. Forsyth CB, Cole A, Murphy G, Bienias JL, Im HJ, Loeser RF Jr (2005) Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli. J Gerontol A Biol Sci Med Sci 60:1118–1124

    PubMed  Google Scholar 

  29. Long D, Blake S, Song XY, Lark M, Loeser RF (2008) Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13. Arthritis Res Ther 10:R23

    Google Scholar 

  30. Guerne PA, Blanco F, Kaelin A, Desgeorges A, Lotz M (1995) Growth factor responsiveness of human articular chondrocytes in aging and development. Arthritis Rheum 38:960–968

    Article  PubMed  CAS  Google Scholar 

  31. Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O (2007) A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Jt Surg Am 89:2105–2112

    Article  Google Scholar 

  32. Krishnan SP, Skinner JA, Bartlett W, Carrington RW, Flanagan AM, Briggs TW, Bentley G (2006) Who is the ideal candidate for autologous chondrocyte implantation? J Bone Jt Surg Br 88:61–64

    Article  CAS  Google Scholar 

  33. Leutert G (1980) Morphological aging changes in human articular cartilage. Mech Ageing Dev 14:469–475

    Article  PubMed  CAS  Google Scholar 

  34. Brew CJ, Clegg PD, Boot-Handford RP, Andrew JG, Hardingham T (2010) Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy. Ann Rheum Dis 69:234–240

    Article  PubMed  CAS  Google Scholar 

  35. Schiphof D, Boers M, Bierma-Zeinstra SM (2008) Differences in descriptions of Kellgren and Lawrence grades of knee osteoarthritis. Ann Rheum Dis 67:1034–1036

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Dr. A. Baranowsky (Department for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany) for the performance of the histology presented in Fig. 2. This study’s funding source was not involved in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication.

Conflict of interest

PN received grants and fees for educational purposes from TiGenix and Stryker.

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Authors and Affiliations

  1. Department for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Jan M. Pestka

  2. Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Hugstetter Str. 55, 79106, Freiburg, Germany

    Hagen Schmal, Gian Salzmann, Norbert P. Südkamp & Philipp Niemeyer

  3. Metreon Bioproducts GmbH, Freiburg, Germany

    Jochen Hecky

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  1. Jan M. Pestka
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  2. Hagen Schmal
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Correspondence to Philipp Niemeyer.

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Pestka, J.M., Schmal, H., Salzmann, G. et al. In vitro cell quality of articular chondrocytes assigned for autologous implantation in dependence of specific patient characteristics. Arch Orthop Trauma Surg 131, 779–789 (2011). https://doi.org/10.1007/s00402-010-1219-8

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  • DOI: https://doi.org/10.1007/s00402-010-1219-8

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