Fibroblast induced cartilage destruction in SCID mice

 

Figure 1: Handling of the SCID mice during a transplantation study.

A: Transplantation of invasive fibroblasts into the knee joint of a SCID mouse.

B: Measurement of the thickness of the knee joint of a SCID mouse by caliper.

Species

Mouse

Field of application

The cartilage destruction model is used to investigate pathophysiological processes in the knee joint as seen in rheumatoid arthritis (RA) or other cartilage degenerative diseases. The cartilage destruction is induced by the transplantation of a murine invasive fibroblast cell line into the knee joint of SCID mice. The resulting destruction is characterized by cell invasion into the cartilage and formation of a pannus. This model gives the opportunity to analyse processes leading to cartilage destruction by synovial fibroblasts. The potential of possible treatment options can be assessed.

  • Pharmacodynamics and pharmacokinetics
  • (Patho)physiological processes
  • Therapeutic efficacy
  • Proof of concept

Endpoints/Outcome parameter

  • Joint thickness (in vivo)
  • Immune cells in full blood (in vivo)
  • Cytokines and other protein levels in blood plasma (in vivo)
  • Swelling, destruction, pannus formation, immune cell infiltration (ex vivo)

Readout parameter

  • Measurement by means of a caliper
  • Flow cytometry
  • ELISA/CBA (cytometric bead array)
  • RT-PCR
  • Western Blot
  • Histology (various classical histological stains)

Quality management measures

  • Controls
  • Blinded induction
  • Blinded data collection and analysis
  • Randomisation
  • Allocation concealment
  • Biometric Expertise
  • Internal quality management

References

  • Treese C, Mittag A, Lange F, Tarnok A, Loesche A, Emmrich F, Lehmann J, Sack U. Characterization of fibroblasts responsible for cartilage destruction in arthritis. Cytometry A. 2008; 73(4):351-60.

  • Lange F, Härtl S, Ungethuem U, Kuban RJ, Hammerschmidt S, Faber S, Morawietz L, Wirtz H, Emmrich F, Krenn V, Sack U. Anti-TNF effects on destructive fibroblasts depend on mechanical stress. Scand J Immunol. 2006; 64(5):544-53.

  • Sack U, Sehm B, Kahlenberg F, Murr A, Lehmann J, Tannapfel A, Uberla K, Moessner A, Dietrich A, Emmrich F, Lange F, Jungel A, Braun JM, Anderegg U. Investigation of arthritic joint destruction by a novel fibroblast-based model. Ann N Y Acad Sci. 2005; 1051:291-8.

  • Sack U, Hirth A, Funke B, Wiedemeyer K, Lange F, Tröltzsch M, Tannapfel A, Gebhardt R, Emmrich F, Lehmann J. A novel model of fibroblast-mediated cartilage destruction. Scand J Immunol. 2005; 61(1):18-28.

  • Lange F, Bajtner E, Rintisch C, Nandakumar KS, Sack U, Holmdahl R. Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis. Ann Rheum Dis. 2005; 64(4):599-605.