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

Objective. To investigate the microenvironment of bone marrow (BM) of patie nts with rheumatoid arthritis (RA). Methods. Nurse cell-like BM stromal cell lines were established from BM mon onuclear cells of patients with RA. We examined the various characteristics of these cell lines, including morphology, pseudoemperipolesis activity, c ell surface markers, cytokine production and hyaluronan (I-LA) production. Results. These RA BM nurse cell-like lines (RA-BMNC) were of mesenchymal or igin and positive for CD44, CD54 and HLA-DR. They were defined as nurse cel ls because of pseudoemperipolesis activity that allowed lymphocytes to migr ate underneath. RA-BMNC lines produced WA and multiple cytokines including interleukin (IL)-6, IL-7, IL-8 and granulocyte-macrophage colony-stimulatin g factor (GM-CSF). WA production by BM stromal cells was correlated with ps eudoemperipolesis activity. RA-BMNC produced significantly higher levels of IL-6, IL-8 and GM-CSF by co-culture with lymphocytes. The cells also produ ced IL-1 beta, G-CSF and tumour necrosis factor only when co-cultured with lymphocytes. The RA-BMNC maintained the growth of CD14+ myeloid cells uniqu e 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.