A new model for rheumatoid arthritis generated by engraftment of rheumatoid synovial tissue and normal human cartilage into scid mice

Abstract

Objective. A new animal model was used to study the interaction between rheumatoid synovial cells and cartilage and to explore the cellular basis of rheumatoid joint destruction.Methods. Fresh synovial tissue derived from patients with rheumatoid arthritis was implanted with normal human cartilage into SCID mice, either subcutaneously or under the renal capsule, for up to 304 days. The implants were analyzed by light and electron microscopy, as well as by immunohistochemistry and in situ hybridization.Results. Human synovial tissue and cartilage implanted in SCID mice are maintained by the animals for up to 304 days. After 35 days, focal erosions occur at the site of attachment of synovial lining cells to the cartilage. After 105 days, a pannus-like formation, consisting of proliferating synovial fibrpblast-like cells invading the cartilage, is observed. The fibroblast nature of these cells was supported by observation of only focal expression of the macrophage markers CD14 and CD68. Cells at the immediate site of cartilage destruction express messenger RNA for cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial regions away from the site of destruction. The human origin of the tissue involved in cartilage destruction was

Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus

“…After 4 weeks of culture, only scattered T cells were detected. This is consistent with the in vivo data presented by Rendt et a1 and Geiler et a1 (20,22).…”

“…This may be explained by the fact that the chondrocyte matrix, although consisting of essentially the same components as native cartilage, was possibly not as dense. We believe this feature is rather advantageous, since it allows us to observe an invasion after only several weeks, compared with the conditions in the SCID mouse model, where up to 6 months are necessary to verify an invasion of the cartilage (22). It is not clear why the invasion slowed down after 21 days in the interactive RA synovial cell/ chondrocyte culture.…”

“…RA synovial membrane preserves its characteristic features and destructive potential when implanted into SCID mice (22). We were able to cultivate synovial membrane explants under conventional culture conditions for an average period of 4 weeks and to retain the structural integrity of the tissue without a detectable degree of necrosis.…”

CXCL16‐mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway

“…This model has been used successfully by other groups to show that engrafted RA ST not only keeps many of the morphologic and pathologic characteristics of RA ST (62), but also can be used as an appropriate model of RA (63). We found that tail vein-injected cells migrate to engrafted RA ST and murine LNs in response to intragraft injections of human CXCL16.…”

Induction of apoptosis in the rheumatoid synovium by Fas ligand gene transfer

“…18 In addition, engraftment of human rheumatoid synovium into the knee joint of SCID mice can cause arthritis 28 and the implant can reproduce the biologic characteristics of destruction of the normal cartilage of humans. 29 Engraftment of human rheumatoid synovium into the back muscle of SCID mice (SCID-RA) also preserved the histologic components of rheumatoid synovia. In our approach using gene therapy for RA employing the SCID-RA system, we showed that local injection of irradiated-hFasL transfectants resulted in elimination of Fas-positive synoviocytes, CD3 + , CD20 + and CD68 + cells from the rheumatoid synovium due to the induction of apoptosis without any extra immune response by xenotransplantation or bystander cytotoxicity of transfectants against host tissues.…”