Abstract
Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSC-treated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADSCs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA.
Highlights
Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties
After intra-articular injection of ADSCs, the thickness of the synovium and inflammatory cell infiltration in the knee were reduced in the mice with laminarin-induced arthritis (Fig. 2D,E)
We found that localized injection of ADSC cells and spheroids reduces intra-articular inflammation and regenerates damaged cartilage in a mouse model of rheumatoid arthritis (RA)
Summary
Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and degeneration of articular cartilage and bone. An effective localized treatment has yet to be demonstrated in a mouse model of RA using ADSCs. In addition, three-dimensional (3D) culturing reportedly increases the therapeutic effects of MSCs in vitro[16]. SKG mice develop T cell-mediated chronic autoimmune polyarthritis, characterized by joint inflammation and articular cartilage degeneration[18,19] that is strikingly similar to the clinical progression of RA in humans. We hypothesized that localized therapy using ADSC single cells and 3D cultured ADSC spheroids might be effective for the treatment of RA.
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