Background/Purpose: Adipose derived stem cell (ADSC) is one of the stem cells produced by adipose tissue which can be collected easily and in large quantities. It has been reported the anti-inflammatory effect of ADSC in some disease models. However, the effect of ADSC for synovitis such as rheumatoid arthritis (RA) is unknown. The aim of this study is to investigate the effects of ADSC for intraarticular synovitis and cartilage degeneration in SKG/Jcl mice in vivo and the effects of ADSC for synovial fibroblast in vitro.

Methods: SKG/Jcl mice which developed auto-immune arthritis by adjuvant stimulation were used as RA animal model. In vivo, the intra-articular injections of ADSC or PBS were performed to the bilateral knee of SKG mice with arthritis. The knee joint was histologically assessed with synovitis score and Mankin score at week 2 after ADSC injection. In vitro, the anti-inflammatory effect of ADSC for stimulated human synovial fibroblast was analyzed by real-time RT-PCR.

Results: In vivo, the synovitis score and Mankin score were significantly lower in ADSC group (synovitis score 2.0 } 0.7 vs 6.0 } 1.6, p<0.01 and Mankin score 2.2 } 0.8 vs 4.9 } 0.8, p<0.01) (Figure 1). Surprisingly, the cartilage degeneration was repaired in ADSC group (Figure 2). As a comparison, glucocorticoid injection suppressed the synovial inflammation but cartilage degeneration was not improved (Figure 2). In vitro, the expression of tumor necrosis factor-stimulated gene-6 (TSG-6), the anti-inflammatory cytokine, was significantly higher in ADSC than in synovial cell (p<0.01). The inflammatory cytokine levels in stimulated synovial cell were significantly decreased by ADSC treatment (p<0.01).

Figure 1. The anti-inflammatory effects of intra-articular ADSC injection.

The H-E stain of knee joint in SKG/Jcl mice (a) and PBS treated SKG/Jcl mice after induction of synovitis (b). The synovial proliferation was suppressed in ADSC treated SKG/Jcl mice after induction of synovitis (c). The Safranin-O stain in SKG/Jcl mice without synovitis (d), PBS treated SKG/Jcl mice (e) and ADSC treated SKG/Jcl mice (f) after induction of synovitis. The cartilage staining was reduced in SKG/Jcl mice with inflammatory synovitis (yellow arrows).

Figure 2. Cartilage repair in ADSC group

Conclusion: This is the first report to show the anti-inflammatory effect of ADSC for synovitis in RA animal model. ADSC can be collected with a minimally invasive technique more easily than other mesenchymal stem cells. ADSC might have potential to be one of the RA treatment and repair cartilage degeneration.