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Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo

  • Experimental Study
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

Purpose

The combination of chondrogenic factors might be necessary to adequately stimulate articular cartilage repair. In previous studies, enhanced repair was observed following transplantation of chondrocytes overexpressing human insulin-like growth factor I (IGF-I) or fibroblast growth factor 2 (FGF-2). Here, the hypothesis that co-overexpression of IGF-I and FGF-2 by transplanted articular chondrocytes enhances the early repair of cartilage defects in vivo and protects the neighbouring cartilage from degeneration was tested.

Methods

Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or co-transfected with the IGF-I and FGF-2 gene, encapsulated in alginate and transplanted into osteochondral defects in the knee joints of rabbits in vivo.

Results

After 3 weeks, co-overexpression of IGF-I/FGF-2 improved the macroscopic aspect of defects without affecting the synovial membrane. Immunoreactivity to type-I collagen, an indicator of fibrocartilage, was significantly lower in defects receiving IGF-I/FGF-2 implants. Importantly, combined IGF-I/FGF-2 overexpression significantly improved the histological repair score. Most remarkably, such enhanced cartilage repair was correlated with a 2.1-fold higher proteoglycan content of the repair tissue. Finally, there were less degenerative changes in the cartilage adjacent to the defects treated with IGF-I/FGF-2 implants.

Conclusion

The data demonstrate that combined gene delivery of therapeutic growth factors to cartilage defects may have value to promote cartilage repair. The results also suggest a protective effect of IGF-I/FGF-2 co-overexpression on the neighbouring articular cartilage. These findings support the concept of implementing gene transfer strategies for articular cartilage repair in a clinical setting.

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Acknowledgments

Supported by the Deutsche Forschungsgemeinschaft (DFG MA 2363/1-2 to H.M.). The authors thank E. Kabiljagic and E. Gluding for expert technical assistance.

Conflict of interest

The authors declare no competing financial interests. The authors, their immediate families and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article.

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Authors and Affiliations

  1. Experimental Orthopaedics and Osteoarthritis Research, Saarland University, Kirrbergerstrasse, Building 37, 66421, Homburg, Germany

    Patrick Orth, Gunter Kaul, Magali Cucchiarini & Henning Madry

  2. Department of Orthopaedic Surgery, Saarland University Medical Center, Kirrbergerstrasse, Building 37, 66421, Homburg, Germany

    Patrick Orth, Dieter Kohn & Henning Madry

  3. Department of Biostatistics, Children’s Hospital, Harvard University, 300 Longwood Ave, Boston, MA, 02115, USA

    David Zurakowski

  4. Institute for Experimental Surgery, Saarland University Medical Center, Kirrbergerstrasse, Building 66, 66421, Homburg, Germany

    Michael D. Menger

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  1. Patrick Orth
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  2. Gunter Kaul
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  3. Magali Cucchiarini
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Correspondence to Henning Madry.

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Orth, P., Kaul, G., Cucchiarini, M. et al. Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo. Knee Surg Sports Traumatol Arthrosc 19, 2119–2130 (2011). https://doi.org/10.1007/s00167-011-1448-6

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  • DOI: https://doi.org/10.1007/s00167-011-1448-6

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