Biologic Aspects of Nurse-Like Cells Found in Bone Marrow and Synovial Tissue of Rheumatoid Arthritis Patients

Using collagen-induced arthritis (CIA) rats, we studied the origin of synovial stromal cells, which rapidly appeared and proliferated in joints at the onset of inflammatory polyarthritis, we partially labelled the bone marrow stromal cells (BMSC) with fluorescent dye or 3H-Tdr,and analyzed the migration of labelled BMSC after the immunization with collagen. At the onset of CIA, BMSC migrated through small canals from the bone marrow into the affected joint cavities and seemed to contribute to synovial proliferation in joints [4].

Based on the data above, we were interested in establishing and characterizing the nurse cell-like stromal cells (NCs) in bone marrow (RA-BMNC) as well as those in synovial tissue of rheumatoid arthritis (RA) patients (RA-SNC). RA-BMNC showed the characteristic cell-cell contact with lymphocytes (pseudoempeliporesis), resulting in mutual biologic activation, such as maintaining infiltrating lymphocytes and producing large amount of cytokines. Those were very similar to the reactions of RA-SNC reported in our latest paper [2].

Another point of interest was whether NCs could invade the bone, resulting in erosive changes characteristically observed in RA patients. Although NCs (both RA-SNC and RA-BMNC) were shown to produce IL-6, IL-8, and other cytokines, these were not thought to contribute directly to bone erosion. By co-culturing NCs with lymphocytes, we found activation in the production of MMP-1 and MMP-3, and in the expression of mRNA of both MMP-9 and cathepsin-K. Thus, NCs could be thought to contribute directly to bone erosion in RA patients.