Pretreatment with IL-1β enhances proliferation and chondrogenic potential of synovium-derived mesenchymal stem cells

Background aims. Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage regeneration because of their high proliferative ability and chondrogenic potential. We have performed clinical trials using synovial MSCs to regenerate articular cartilage. To achieve good clinical outcomes for cell transplantation therapy, it is important to control both quantity (cell number) and quality (pluripotency or chondrogenic potential) of the cells for transplantation. Interleukin (IL)-1 beta is a pro-inflammatory cytokine with significant pro-proliferative potential for mesenchymal cells. However, the effects of IL-1 beta on synovial MSCs remain unknown. We investigated the effects of pretreatment with IL-1 beta on synovial MSCs. Methods. Human synovial tissue was harvested during total knee arthroplasty. Nucleated cells were plated and cultured in the absence or presence of IL-1 beta at 10(-13), 10(-12), 10(-11), 10(-10), 10(-9) or 10(-8) g/mL for 14 days. Results. The number of synovial MSCs increased in a concentration-dependent manner. When cultured for 21 days in chondrogenic medium after pretreatment with 10(-8) g/mL IL-1 beta, pellet aggregation was observed, whereas pretreatment with 10(-12), 10(-11) or 10(-10) g/mL IL-1 beta significantly increased the weight of cartilage pellets (P < 0.01). Surface markers for adhesion ability and pluripotency were reduced with high concentrations of IL-1 beta. IL-6 and IL-8 expression increased, but no changes in the expression level of growth factors were indicated by cytokine array. Conclusions. We have demonstrated that pretreatment of IL-1 beta increased the proliferation and chondrogenic potential of synovial MSCs, which may promote the regenerative potential of synovial MSCs.