Abstract
Background Umbilical cord mesenchymal stem cells (UCMSC) derived exosomes could simulate the function of MSC and avoid the limitations of MSC, which is being hotspot in the research of rheumatoid arthritis (RA) treatment. Chemokines can recruit inflammatory cells and osteoclasts in inflammatory joints, and participate in the synovial inflammation and bone destruction of RA. The mechanisms of UCMSC- derived exosomes on chemokines have less understood in RA Objectives The aim of this study was to investigate the effect of UCMSC and UCMSC-derived exosomes on the chemokines CCL2, CXCL10 and CXCL12 in CIA rats. Methods Human umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and separated using a differential centrifugation methods. The CIA rats model was set up by freund’s complete adjuvant and type II collagen, then randomly divided into control, CIA, MTX, UCMSCs, UCMSCs exosomes low and high concentration groups. Rats in UCMSCs group were injected in double ankle joint with UCMSCs 2X106/L weekly for 3 weeks. Rats in UCMSCs exosomes low and high group were injected in double ankle joint with UCMSCs exosomes 30μg and 90μg weekly for 3 weeks, respectively. Rats in MTX group were given intraperitoneal injection with MTX (0.9mg/kg) weekly for 3 weeks. Serum concentrations of CCL2 and CXCL10 were detected by flow cytometry. CXCL12 serum level was tested by enzyme-linked immunosorbent assay (ELISA). The protein expressions of CCL2, CXCL10 and CXCL12 in synovial tissue were detected by immunohistochemistry. CCL2, CXCL10 and CXCL12 mRNA levels in synovial joint and spleen were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results Intra-articular injection of UCMSC exosomes decreased CCL2 and CXCL12 levels in serum and improved synovial hyperplasia and inflammatory cell infiltration in the CIA rats. UCMSC exosomes suppressed the protein expressions of CCL2, CXCL10, CXCL12 in synovial tissue. It also inhibited transcript levels of CCL2, CXCL10, CXCL12 in synovial tissue and spleen. UCMSC had similar effect on CCL2, CXCL10, CXCL12 in CIA. The high concentration group was more effective than the low concentration in preventing CCL2,CXCL10,CXCL12 protein expressions of synovial tissue and CCL2 transcript level of spleen. Conclusion UCMSC exosomes alleviates synovial inflammation in CIA rats through suppression of CCL2, CXCL10, CXCL12 release. The inhibitory effect of on chemokines simulate UCMSC, their cell of origin, the high concentration was better than low concentration.
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