Skip to main content
SpringerLink
Log in

Cell manipulation in autologous chondrocyte implantation: from research to cleanroom

  • Original Article
  • Published:
La Chirurgia degli Organi di Movimento Aims and scope Submit manuscript

Abstract

In the field of orthopaedics, autologous chondrocyte implantation is a technique currently used for the regeneration of damaged articular cartilage. There is evidence of the neo-formation of tissue displaying characteristics similar to hyaline cartilage. In vitro chondrocyte manipulation is a crucial phase of this therapeutic treatment consisting of different steps: cell isolation from a cartilage biopsy, expansion in monolayer culture and growth onto a three-dimensional biomaterial to implant in the damaged area. To minimise the risk of in vitro cell contamination, the manipulation must be performed in a controlled environment such as a cleanroom. Moreover, the choice of reagents and raw material suitable for clinical use in humans and the translation of research protocols into standardised production processes are important. In this study we describe the preliminary results obtained by the development of chondrocyte manipulation protocols (isolation and monolayer expansion) in cleanrooms for the application of autologous implantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brittberg M, Winalski CS (2003) Evaluation of cartilage injuries and repair. J Bone Joint Surg Am 85[Suppl 2]:58–69

    PubMed  Google Scholar 

  2. Frenkel SR, Di Cesare PD (1999) Degradation and repair of articular cartilage. Front Biosci 4:671–685

    Article  Google Scholar 

  3. Kuettner KE (1992) Biochemistry of articular cartilage in health ad disease. Clin Biochem 25:155–163

    Article  PubMed  CAS  Google Scholar 

  4. Gross AE (2002) Repair of cartilage defects in the knee. J Knee Surg 15:167–169

    PubMed  Google Scholar 

  5. Minas T, Nehrer S (1997) Current concepts in the treatment of articular cartilage defects. Orthopedics 20:525–538

    PubMed  CAS  Google Scholar 

  6. Erggelet C, Steinwachs MR, Reichelt A (2000) The operative treatment of full thickness cartilage defects in the knee joint with autologous chondrocyte transplantation. Saudi Med J 21:715–721

    PubMed  CAS  Google Scholar 

  7. Nathwani AC, Benjamin R, Nienhuis AW, Davidoff AM (2004) Current status and prospects for gene therapy. Vox Sang 87:73–81

    Article  PubMed  CAS  Google Scholar 

  8. Sasaki T, Fujimoto K, Sakai K et al (2003) Gene and cell-based therapy for diabetes mellitus: endocrine gene therapeutics. Endocr Pathol 14:141–144

    Article  PubMed  CAS  Google Scholar 

  9. Brittberg M, Lindhal A, Olhlsson C et al (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 

  10. Brittberg M, Peterson L, Sjogren-Jansson E et al (2003) Articular cartilage engineering with autologous chondrocyte transplantation. A review of recent developments. J Bone Joint Surg Am 85[Suppl 3]:109–115

    PubMed  Google Scholar 

  11. Peterson L, Minas T, Brittberg M et al (2000) Two-to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374:212–234

    Article  PubMed  Google Scholar 

  12. Peterson L, Minas T, Brittberg M, Lindahl A (2003) Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years. J Bone Joint Surg Am 85[Suppl 2]:17–24

    PubMed  Google Scholar 

  13. Giannini S, Buda R, Grigolo B et al (2005) The detached osteochondral fragment as a source of cells for autologous chondrocyte implantation (ACI) in the ankle joint. Osteoarthritis Cartilage 13:601–607

    Article  PubMed  CAS  Google Scholar 

  14. Marcacci M, Berruto M, Brocchetta D et al (2005) Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 435:96–105

    Article  PubMed  Google Scholar 

  15. Grigolo B, Roseti L, Fiorini M et al (2002) Applicazioni dell’ingegneria tissutale: riparazione di lesioni cartilaginee con condrociti autologhi. Reumatismo 54:364–371

    PubMed  CAS  Google Scholar 

  16. — (2004) European Pharmacopoeia 5.0

  17. EC Guide to Good Manufacturing Practice — Revision to Annex 1, “Manufacture of sterile medicinal products”

  18. ISO 14644, “Cleanrooms and associated controlled environments”

  19. — (1998) UNI EN 1822 “High efficiency air filter (HEPA and ULPA)”, April

  20. ISO 14698, “Cleanrooms and associated controlled environments — Biocontamination control”

  21. — (2001) UNI EN 12469 “Criteri di prestazione per le postazioni di sicurezza microbiologica”

  22. Patwari P, Fay J, Cook MN et al (2001) In vitro models for investigation of the effects of acute mechanical injury on cartilage. Clin Orthop Relat Res 391[Suppl]:S61–S71

    Article  PubMed  Google Scholar 

  23. Smith RL, Carter DR, Schurman DJ (2004) Pressure and shear differentially alter human articular chondrocyte metabolism: a review. Clin Orthop Relat Res 427[Suppl]:S89–S95

    PubMed  Google Scholar 

  24. Tare RS, Howard D, Pound JC et al (2005) Tissue engineering strategies for cartilage generation—micromass and three dimensional cultures using human chondrocytes and a continuous cell line. Biochem Biophys Res Commun 333:609–621

    Article  PubMed  CAS  Google Scholar 

  25. Pulsatelli L, Dolzani P, Piacentini A et al (1999) Chemokine production by human chondrocytes. J Rheumatol 26:1992–2001

    PubMed  CAS  Google Scholar 

  26. Martin I, Suetterlin R, Baschong W et al (2001) Enhanced cartilage tissue engineering by sequential exposure of chondrocytes to FGF-2 during 2D expansion and BMP-2 during 3D cultivation. J Cell Biochem 83:121–128

    Article  PubMed  CAS  Google Scholar 

  27. Huch K, Stove J, Puhl W, Gunther KP (2002) Review and comparison of culture techniques for articular chondrocytes. Z Orthop Ihre Grenzgeb 140:145–152

    Article  PubMed  CAS  Google Scholar 

  28. Jayme DW, Blackman KE (1985) Culture media for propagation of mammalian cells, viruses, and other biologicals. Adv Biotechnol Processes 5:1–30

    PubMed  CAS  Google Scholar 

  29. Rolleston WB (1999) Bovine serum: reducing the variables through the use of donor herds. Dev Biol Stand 99:79–86

    PubMed  CAS  Google Scholar 

  30. Asher DM (1999) Bovine sera used in the manufacture of biologicals: current concerns and policies of the US. Food and Drug Administration regarding the transmissible spongiform encephalopathies. Dev Biol Stand 99:41–44

    PubMed  CAS  Google Scholar 

  31. Mackensen A, Drager R, Schlesier M et al (2000) Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells. Cancer Immunol Immunother 49:152–156

    Article  PubMed  CAS  Google Scholar 

  32. Shah G (1999) Why do we still use serum in the production of biopharmaceuticals? Dev Biol Stand 99:17–22

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio di Manipolazione Cellulare Estensiva, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy

    Livia Roseti, Marta Serra, Irene Brognara, Annamaria Lopriore & Alessandra Bassi

  2. VII Divisione, Istituto Ortopedico Rizzoli, Bologna, Italy

    Domenico Tigani

  3. Banca del Tessuto Muscolo-Scheletrico, Istituti Ortopedici Rizzoli, Bologna, Italy

    Pier Maria Fornasari

Authors
  1. Livia Roseti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Serra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Domenico Tigani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irene Brognara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annamaria Lopriore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessandra Bassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pier Maria Fornasari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Livia Roseti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roseti, L., Serra, M., Tigani, D. et al. Cell manipulation in autologous chondrocyte implantation: from research to cleanroom. Chir Organi Mov 91, 147–151 (2008). https://doi.org/10.1007/s12306-007-0024-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12306-007-0024-1

Keywords

Search

Navigation