Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2880
Knedla, A; Riepl, B; Lefèvre, S; Kistella, S; Grifka, J; Straub, R H; Gay, S; Schölmerich, J; Müller-Ladner, U; Neumann, E (2009). The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mouse model for rheumatoid arthritis. Annals of the Rheumatic Diseases, 68(1):124-129.
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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(R) Osmotic Miniature Pump Model 2004 containing 200 microl 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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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine|
|Dewey Decimal Classification:||610 Medicine & health|
|Date:||13 February 2009|
|Deposited On:||05 Aug 2008 07:35|
|Last Modified:||27 Nov 2013 19:22|
|Publisher:||BMJ Publishing Group|
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