【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.
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.
Objectives: Mesenchymal stem cells (MSCs) are considered as a possible tool for treatment of rheumatoid arthritis (RA) due to their immunoregulatory ability and pluripotency. Here we established an effective delivery system of MSCs on a arthritis animal model. Methods: MSCs were seeded on poly-lactic-co-glycollic acid (PLGA) scaffold then implanted into ankles (IMP) of collagen induced arthritis (CIA) rats or simply injected intra-articularly (IA) or intra-peritoneally (IP). Results: IMP to bilateral ankles significantly suppressed the severity of arthritis evaluated by arthritis score, hind paw thickness and body weight compared to CIA, while IA and IP showed less or no effect. Accordingly, bone destruction detected by X-ray, micro CT and infiltration of inflammatory cells, damage of cartilage and bone destruction detected histologically were reduced in IMP group but not in other groups. Furthermore, the size of the draining lymph nodes was smaller with reduced germinal center formation in the IMP group. Conclusion: Implantation of MSCs with nano-fiber scaffold efficiently suppressed arthritis and bone destruction, suggesting a novel MSCs delivery system for future RA treatment.