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Articular cartilage repair by genetically modified bone marrow aspirate in sheep

Gene Therapy volume 17, pages 779–789 (2010)Cite this article

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Abstract

Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-β1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-β1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.

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Acknowledgements

We thank Pierre Mainil-Varlet, MD, PhD, Davor Jezek, MD, PhD, Andreja Vukasovic and Ivan Cerovecki for assistance in histological analysis; Snjezana Martinovic, MD, PhD for valuable insight in designing this study; Mario Kreszinger, DVM, PhD, Drazen Vnuk, DVM, PhD, and Norbert Kastner, MD, for assistance during animal surgeries; and Fran Borovecki, MD, PhD, for his work with PCR analysis. This study was supported by the Croatian Ministry of Science (projects No. 108-0000000-3652 and 108-1080327-0161). Marko Loparic acknowledges an NCCR ‘Nanoscale Science’ grant, awarded by the Swiss National Science Foundation to Ueli Aebi and Ivan Martin.

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Authors and Affiliations

  1. University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia

    A Ivkovic

  2. Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria

    A Pascher & R Windhager

  3. University Hospital for Traumatology, School of Medicine, University of Zagreb, Zagreb, Croatia

    D Hudetz

  4. Department of Surgery, Orthopaedics and Ophthalmology, Veterinary School, University of Zagreb, Zagreb, Croatia

    D Maticic

  5. Department of Orthopaedic Surgery, University Hospital Center Zagreb, Zagreb, Croatia

    M Jelic

  6. Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, UK

    S Dickinson

  7. Departments of Surgery and Biomedicine, University Hospital Basel, Basel, Switzerland

    M Loparic

  8. ME Mueller Institute for Structural Biology, Biozentrum University of Basel, Basel, Switzerland,

    M Loparic

  9. Special Hospital for Orthopaedic Surgery ‘Akromion’, Krapinske Toplice, Croatia

    M Haspl

  10. Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia

    M Pecina

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  1. A Ivkovic
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Correspondence to A Ivkovic.

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Ivkovic, A., Pascher, A., Hudetz, D. et al. Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther 17, 779–789 (2010). https://doi.org/10.1038/gt.2010.16

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