- Paper Report
- Open Access
SCID mouse model of inflamed RA synovium
- Willemijn van der Laan1
© Biomed Central Ltd 2002
- Received: 28 March 2002
- Published: 28 March 2002
- rheumatoid arthritis
- SCID model
Synovitis in rheumatoid arthritis (RA) involves local activation of lymphocytes, infiltration of inflamatory cells, synovial hyperplasia and angiogenesis. The current animal and in vivo models for RA have their limitations, since they do not reproduce all of the clinical and histopathological features of RA. The aim of the present study was to examine whether synovial tissue taken from RA joints retains its phenotypic and functional features after engraftment in a severe combined immunideficient (SCID) mouse, in order to develop an experimental model that reflects human RA without losing the complexity of RA synovitis.
Synovial tissue was taken from RA patients and either directly snap-frozen or implanted under the skin of SCID mice for 3, 6, or 12 weeks and snap-frozen thereafter for immunohistochemical or molecular analysis. For some experiments, CFSE-labelled enriched T cells were injected in the tail veins.
Similar numbers and types of leukocytes, including lymphocytes, persisted until 12 weeks after engraftment. The grafts underwent reorganisation such that CD68+ myeloid lineage cells were scattered throughout the graft, the lining layer was no longer demarcated and the fibroblasts became denser. Injected T cells migrated and accumulated specifically into the grafts. Human endothelial cells remained activated and markers of angiogenesis were still detectable after 12 weeks of engraftment. B cell and monocyte activity persisted until 60 days.
The authors concluded that the SCID mouse model of RA maintains many of the phenotypic and functional features of the inflamed RA synovium and that this model provides a unique model to examine the interaction of the RA microenvironment with the major components of the inflammatory process.
Geiler T, Kriegsmann J, Keyszer GM, Gay RE, Gay S: A new model for rheumatoid arthritis generated by engraftment of rheumatoid synovial tissue and normal human cartilage into SCID mice. Arthritis Rheum 1994, 37:1664-1671.