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Rheumatology 1999; 38: 854-863
© 1999 British Society for Rheumatology

Establishment of nurse-like stromal cells from bone marrow of patients with rheumatoid arthritis: indication of characteristic bone marrow microenvironment in patients with rheumatoid arthritis

T. Tomita, E. Takeuchi, T. Toyosaki-Maeda1, H. Oku1, M. Kaneko, H. Takano, K. Sugamoto, K. Ohzono, R. Suzuki1 and T. Ochi

Department of Orthopaedic Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871 and
1 Research Unit of Immunology, Shionogi Institute for Medical Science, Shionogi & Co., Ltd, 2-5-1, Mishima, Settu, Osaka 566-0022, Japan

Correspondence to: T. Ochi, Department of Orthopaedic Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan.

Objective. To investigate the microenvironment of bone marrow (BM) of patients with rheumatoid arthritis (RA).

Methods. Nurse cell-like BM stromal cell lines were established from BM mononuclear cells of patients with RA. We examined the various characteristics of these cell lines, including morphology, pseudoemperipolesis activity, cell surface markers, cytokine production and hyaluronan (HA) production.

Results. These RA BM nurse cell-like lines (RA-BMNC) were of mesenchymal origin and positive for CD44, CD54 and HLA-DR. They were defined as nurse cells because of pseudoemperipolesis activity that allowed lymphocytes to migrate underneath. RA-BMNC lines produced HA and multiple cytokines including interleukin (IL)-6, IL-7, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). HA production by BM stromal cells was correlated with pseudoemperipolesis activity. RA-BMNC produced significantly higher levels of IL-6, IL-8 and GM-CSF by co-culture with lymphocytes. The cells also produced IL-1ß, G-CSF and tumour necrosis factor only when co-cultured with lymphocytes. The RA-BMNC maintained the growth of CD14+ myeloid cells unique to severe RA.

Conclusion. The present results both indicate that RA-BMNC are nurse cells and suggest that they may play an important role in the pathogenesis of RA.

KEY WORDS: Rheumatoid arthritis, Nurse-like cells, Bone marrow.


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