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Gene-based approaches for the repair of articular cartilage

Gene Therapy volume 11, pages 351–359 (2004)Cite this article

Abstract

Gene transfer technology has opened novel treatment avenues toward the treatment of damaged musculoskeletal tissues, and may be particularly beneficial to articular cartilage. There is no natural repair mechanism to heal damaged or diseased cartilage. Existing pharmacologic, surgical and cell based treatments may offer temporary relief but are incapable of restoring damaged cartilage to its normal phenotype. Gene transfer provides the capability to achieve sustained, localized presentation of bioactive proteins or gene products to sites of tissue damage. A variety of cDNAs have been cloned which may be used to stimulate biological processes that could improve cartilage healing by (1) inducing mitosis and the synthesis and deposition of cartilage extracellular matrix components by chondrocytes, (2) induction of chondrogenesis by mesenchymal progenitor cells, or (3) inhibiting cellular responses to inflammatory stimuli. The challenge is to adapt this technology into a useful clinical treatment modality. Using different marker genes, the principle of gene delivery to synovium, chondrocytes and mesenchymal progenitor cells has been convincingly demonstrated. Following this, research efforts have begun to move to functional studies. This involves the identification of appropriate gene or gene combinations, incorporation of these cDNAs into appropriate vectors and delivery to specific target cells within the proper biological context to achieve a meaningful therapeutic response. Methods currently being explored range from those as simple as direct delivery of a vector to a cartilage defect, to synthesis of cartilaginous implants through gene-enhanced tissue engineering. Data from recent efficacy studies provide optimism that gene delivery can be harnessed to guide biological processes toward both accelerated and improved articular cartilage repair.

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Acknowledgements

This work was supported in part by the following grants from the Harry M Zweig Memorial Foundation, Grayson Jockey Club Research Foundation, Steadman-Hawkins Sports Medicine Foundation, The Institute for Sports Medicine Research, National Institute of Arthritis and Musculoskeletal and Skin diseases: R03-AR47616, 1R41-AR49632, 1R01-AR050249, 1R01-AR48566, AR-049639 and AR-049159.

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  1. Department of Orthopaedic Surgery, University of Indiana Medical School, Indianapolis, IN, USA

    SB Trippel

  2. Center for Molecular Orthopaedics, Harvard Medical School, Boston, MA, USA

    SC Ghivizzani

  3. Comparative Orthopaedics Laboratory, Cornell University, Ithaca, NY, USA

    AJ Nixon

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Trippel, S., Ghivizzani, S. & Nixon, A. Gene-based approaches for the repair of articular cartilage. Gene Ther 11, 351–359 (2004). https://doi.org/10.1038/sj.gt.3302201

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