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The therapeutic use of osmotic minipumps in the SCID mouse model for rheumatoid arthritis
  1. A Knedla
  1. Justus-Liebig-University of Giessen, Germany
    1. B Riepl
    1. University of Regensburg, Germany
      1. S Lefèvre
      1. Justus-Liebig-University of Giessen, Germany
        1. S Kistella
        1. Justus-Liebig-University of Giessen, Germany
          1. J Grifka
          1. University of Regensburg, Germany
            1. R H Straub
            1. University of Regensburg, Germany
              1. S Gay
              1. University Hospital Zürich, Switzerland
                1. J Schölmerich
                1. University of Regensburg, Germany
                  1. U Müller-Ladner
                  1. Justus-Liebig-University of Giessen, Germany
                    1. E Neumann (e.neumann{at}kerckhoff-klinik.de)
                    1. Justus-Liebig-University of Giessen, Germany

                      Abstract

                      Objectives: The viral gene transfer of Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10) into rheumatoid arthritis (RA) synovial fibroblasts (RASF) showed protective effects on cartilage destruction in the SCID mouse model for RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost- and time-intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID mouse model for RA.

                      Methods: Isolated RASF were cultured for 4 passages and coimplanted together with human cartilage and an Alzet® Osmotic Miniature Pump Model 2004 containing 200 µl of IL-10 and IL-1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL-10 and IL-1ra in murine serum were measured by ELISA.

                      Results: Release of IL-10 and IL-1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL-10 and IL-1ra release showed protective effects towards the co-implanted cartilage, similar to the adenovirally IL-10-/IL-1ra-transduced RASF. The invasion scores for the implants with the osmotic pumps were: invasion 0.7±0.5, degradation 0.5±0.3 (all parameters significant vs. controls, p<0.05).

                      Conclusions: The results demonstrate that the combination of osmotic pumps with the SCID mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.

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