【Objectives】 Mesenchymal stem cells (MSC) possess immunoregulatory ability with osteoblastogenesis which makes them an ideal tool for arthritis treatment. Here we utilized nano-fiber poly-lactic-co-glycolic acid as a scaffold to deliver MSC into arthritic models. 【Methods】 MSC were injected intra-articularly (IA) or intra-peritoneally (IP) or seeded on nano-fiber and implanted into ankles (nano-MSC) of collagen induced arthritis (CIA) rats. 【Results】 Arthritis and bone destruction were significantly suppressed by nano-MSC treatment, while IA or IP demonstrated no effects. Serum anti-type II collagen IgG and the proliferation and cytokine production of CD4+ T cells in nano-MSC rats were significantly decreased compared to control rats. Inoculation of MSC transfected with green fluorescent protein plasmid DNA showed MSC remained within nano-fiber and did not migrate to other organs. MSC cultured on nano-fiber showed increased transforming growth factor (TGF)-β1 production compared to MSC cultured on plate. 【Conclusion】 Administration of MSC with nano-fiber efficiently suppressed arthritis, bone destruction, suggesting a novel MSC delivery system for future arthritis treatment.

To study the precise role of Plasmacytoid dendritic cells (PDCs) and mast cells (MC) in Sjögren's Syndrome (SS). Lip specimen (178 SS vs 7 Sicca) were performed on lymphocytes infiltration, acinar atrophy and intralobular fibrosis. MC, PDCs, CD68 and CXCL13 were detected by IHC or toluidine blue. CXCL13 gene was detected by PCR. Significant lymphocytes infiltration, acinar atrophy and intralobular fibrosis were observed in SS. PDCs and MC were increased in SS than Sicca (p=0.03/0.02). Positive correlation between PDCs with lymphocytes infiltration (p=0.02) and MC with intralobular fibrosis (p=0.03) in primary SS (pSS) was observed. Within the pSS, PDCs correlated with CXCL13+cells, especially CXCL13+macrophages. When macrophages were stimulated with IFN-a in vitro, CXCL13 gene was up-regulated.Our data suggests the specific role of PDCs in lymphocyte infiltration and MCs in intralobular fibrosis of pSS. Therefore, it is likely that PDCs in early stage inducing CXCL13 production from macrophages due to IFN-a contributing to lymphocyte infiltration further constructing germinal centers. In addition, MC seems to be involved in intralobular fibrosis which occurs in mid to late stage of SS.

Mesenchymal stem cells (MSCs) possess immunoregulatory ability with multipotency which makes this cells an ideal tool for treatment of rheumatoid arthritis (RA). Aiming clinical use, the effect of MSCs combined with nano-fiber poly-lactic-co-glycollic acid sheet scaffold (nano-sheet) was assessed. MSCs were injected intra-articularly (IA) or intra-peritoneally (IP) or seeded on nano-sheet and implanted into ankles (IMP) of collagen induced arthritis (CIA) rats. IA or IP treatment demonstrated no effects whereas, IMP significantly suppressed arthritis evaluated by arthritis score and body weight. X-ray, micro-CT and histological analysis revealed markedly suppressed joint destruction with IMP but not with IA or IP. Furthermore, draining lymph nodes were decreased in size and IL-1β expression, serum anti-type II collagen IgG and proliferation of T cell ex vivo was significantly suppressed. Culture of MSCs on Nano-sheet in vitro increased TGF-β1 production while IL-6 was decreased compared to MSCs cultured on plate. Local delivery of MSCs with nano-sheet scaffold efficiently suppressed immune response in CIA. These data suggest the efficacy of nano-sheet with MSCs for RA.