Efficacy of SSEA-3 Positive Cells Derived from Synovial Tissue in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a refractory systemic autoimmune disease with chronic synovial inflammation. Sustained synovial inflammation leads to progressive destruction of bone and cartilage. Treatment to restore joints that have been destroyed irreversibly is not to be established yet even with the recent development of antirheumatic drugs and biological agents. Stage-specific embryonic antigen-3 (SSEA-3), a marker of human embryonic stem (ES) cell, acts as stem cells in the blood. SSEA-3 positive cells derived from RA synovial tissue have higher differentiating abilities than that of SSEA-3 negative cells and inhibitory effects on arthritis in collagen antibody-induced arthritis mice study. SSEA-3 positive cells derived from RA synovial tissue might have the inhibitory effect on arthritis and would be one of the cell sources for new RA treatment. The present manuscript is a brief review of mesenchymal stem cells in RA and described with the potential of RA cell therapy by SSEA-3 positive cells based on our research

Possibility of inhibiting arthritis and joint destruction by SSEA-3 positive cells derived from synovial tissue in rheumatoid arthritis

Aim: Joint destruction progresses irreversibly once they occur in rheumatoid arthritis (RA), even with the recent development of anti-rheumatic drugs. Cells positive for stage-specific embryonic antigen-3 (SSEA-3), a marker of human embryonic stem cell, act as stem cells in the blood. The aim of this study is to investigate the effectiveness of SSEA-3 positive cells for the treatment for RA. Methods: Synovial tissues were harvested at the time of joint surgery in RA patients. Cultured synovial cells were sorted by anti-SSEA-3 antibody using flow cytometry and were analyzed in in vitro. To investigate inhibitory effects on arthritis by SSEA-3 positive cells, collagen antibody-induced arthritis (CAIA) mice were used and transplanted with labeled cells intravenously. Results: Presence of SSEA-3 positive cells was confirmed with approximately 1% in RA synovial cells. SSEA-3 positive cells were negative for CD34 and positive for CD44, CD90 and CD105. Multipotency of SSEA-3 positive cells was higher than that of SSEA-3 negative cells. Arthritis of the group transplanted with SSEA-3 positive cells in CAIA mice decreased over time. Conclusions: SSEA-3 positive cells derived from RA synovial tissue might have the inhibitory effect on arthritis and would be one of cell source for new RA treatment

Insulin secretory defect and insulin resistance in isolated impaired fasting glucose and isolated impaired glucose tolerance

Objective. To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. Methods. We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. Results. In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = - 0.245, p < 0.0001) and had the strongest correlation with 2 h PG (β = - 0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = - 0.162, p < 0.0001) and had the strongest correlation with FPG (β = - 0.214). Conclusions. We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects