ALLOGENEIC BONE MARROW-DERIVED CLONAL MOUSE MARROW STEM CELLS CAN PREVENT COLLAGEN-INDUCED ARTHRITIS

초록

Mesenchymal stem cells (MSCs) have attracted significant attention recently because of their immunomdulatory function, i.e. suppression of T cells. Due to their suppressive role, MSCs have been suggested as novel medical therapeutics to prevent acute graft-versus-host disease (GvHD) or autoimmune diseases. Previously we published a new method to isolate clonal marrow stem cells (cMSCs) from bone marrow aspirates, called subfractionation culturing method (SCM). Using these cMSCs, we investigated whether these cMSCs can prevent collagen-induced arthritis, a mouse model for human rheumatoid arthritis. First, we confirmed that these cMSCs are capable of differentiating into adipocytes, osteocytes and chondrocytes and also suppressing allogeneic T-cell proliferation significantly. Next, we injected cMSCs intra-veinously into DBA/1 mice 10 days after the first immunization with collagen plus complete freund’s adjuvant (CFA). Every other day, 1 x 105 cMSCs have been injected for five times and second immunization was performed at day 21 and then the development of disease has been monitored up to 2 months. The results showed that the disease on-set has been delayed in the cMSC received mice and the disease development was significantly decreased compared to PBS received control mice. Using H&E staining we could confirm that the joints from cMSC received mice have much less cell infiltration. Our results strongly suggest an effective new therapeutic approach of using allogeneic clonal MSCs to target the autoimmune arthritis. However, the molecular mechanism(s) of the therapeutic effect should be further studied.