Human synovial cells from patients with rheumatoid arthritis were transferr
ed to four strains of severe combined immunodeficient (SCID) mice. C.B-17-S
CID, BALB/cA-SCID, BALB/cA-bg-SCID (beige gene: low natural killer cell act
ivity) and RAG2-deficient mice were studied. Synovial tissue-infiltrating c
ells were obtained from an explant culture of synovial tissues derived from
patients with rheumatoid arthritis. Synovial tissue-infiltrating cells wer
e injected into the right knee and dorsal side of foot joint of the animals
at 6 weeks of age. Five weeks after the injection, a histopathological stu
dy was carried out under light microscope. The study revealed evidence that
transplanted human cells made characteristic lesions in the mice, i.e., mu
ltiplication of synovial cells, proliferation of fibroblasts, fibrin exudat
ion neovascularization, bone and cartilage replacement by connective tissue
, and pannus formation. The most remarkable and characteristic lesions were
observed in RAG2-deficient mice, then BALB/cA-bg-SCID, BALB/cA-SCID and C.
B-17-SCID mice, respectively. A highly reproducible experimental animal mod
el of arthritis was established by human synovial cells under in vivo trans
fer circumstances. It is possible that the human/RAG2 chimeric model is use
ful for studies on the pathogenesis of arthritis and the development or eva
luation of therapeutic agents.