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Local immunomodulation with CD4 and CD8 antibodies, but not cyclosporine A, improves osteogenesis induced by ADhBMP9 gene therapy

Gene Therapy volume 12, pages 1235–1241 (2005)Cite this article

Abstract

This study was designed to see if immunosuppression achieved using local application of cyclosporine A (Cs. A) or CD4 and CD8 antibodies would improve bone formation following intramuscular injections of human BMP-4 and BMP-9 adenoviral vectors (ADhBMP4 and ADhBMP9) in Sprague–Dawley rats. Cs. A was injected into the thigh muscle. After 2 days, ADhBMP4, ADhBMP9, and the antibodies were separately injected into the left and right rear legs. At this time, the number of CD4+/CD3+ cells was significantly lower and the number of CD8+/CD3+ cells higher in the Cs. A group than in the control group (P<0.01). The total number of white blood cells 3 days following injection of CD4 and CD8 antibodies was significantly lower than that before the injection (P<0.01). At 4 weeks after the viral and antibody injections, mean bone volumes at the ADhBMP9 treatment sites were 0.29±0.01 cm3 in the viral control group, 0.17±0.03 cm3 in the Cs. A-ADhBMPs group, and 0.59±0.07 cm3 in the antibodies-ADhBMPs group. ADhBMP4 did not induce new bone formation in any group. This study demonstrates that local immunomodulation may improve the osteogenic potential of bone morphogenetic protein gene therapy in the clinical setting.

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Acknowledgements

This project was supported by National Institutes of Health Grant No. R01 AR046488-02, ‘Tissue Engineering Utilizing BMP Gene Therapy’ (Gregory A Helm, MD, PhD, Principle Investigator).

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Author notes

  1. H Li

    Present address: Department of Physiology and Functional Genomics, College of Medicine and McKnight Brain Institute, University of Florida, Gainesville, FL, 32610, USA

Authors and Affiliations

  1. Department of Neurological Surgery, University of Virginia Health System, Charlottesville, 22908, VA, USA

    J Z Li, H Li, G R Hankins, B Dunford & G A Helm

  2. Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, 22908, VA, USA

    G A Helm

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  1. J Z Li
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  3. G R Hankins
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Li, J., Li, H., Hankins, G. et al. Local immunomodulation with CD4 and CD8 antibodies, but not cyclosporine A, improves osteogenesis induced by ADhBMP9 gene therapy. Gene Ther 12, 1235–1241 (2005). https://doi.org/10.1038/sj.gt.3302502

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  • DOI: https://doi.org/10.1038/sj.gt.3302502

Keywords

  • CD4 and CD8 antibodies
  • cyclosporine A
  • immunomulation
  • osteogenic
  • adenovirus
  • bone morphogenetic proteins

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