Therapeutic Effect Of Exosomes From Human Synovial Mesenchymal Stem Cells On Lumbar Facet Osteoarthritis In Mice

Objective:To investigate the therapeutic effect of exosomes from human synovial mesenchymal stem cells on lumbar facet osteoarthritis in mice.Methods:Forty-four 6-week-old male mice(C57BL/6)were randomly divided into 4 groups: Control group(n = 11),Stand group(n = 11),PBS group(n= 11)and Exosomes group(n = 11).Control group: without any treatment,Stand group: mice stood for ten weeks,PBS group: mice stood for ten weeks,during the last 4 weeks,mice injected PBS twice a week,Exosomes group: mice stood for ten weeks,during the last 4 weeks,mice injected human synovial mesenchymal stem cells exosomes twice a week.At the10 th week of the experiment,all mice were killed,the lumbar in each group(n=10)were collected,and Micro-CT was used to analyze the lumbar facet joints.After decalcification,the lumbar facet joints were stained with saffron fast green,Trap and immunohistochemistry.OARSI score was used to quantify the grade of facet joint degeneration,the ACAN and COL II was detected by immunohistochemistry,and the expression of CD68+CD206,CD68+CD86,CD31,CGRP and MMP13 was detected by immunofluorescence.Results:1.The OARSI score of lumbar facet articular cartilage showed that the score of stand group was significantly higher than that of Control group(P < 0.05),and the OARSI score of Exosomes group was significantly lower than that of PBS group(P < 0.05).2.Micro-CT: compared with the Control group,BV/TV,Tb.Th and Tb.N were decreased,while BS/BV and Tb.Sp were increased significantly in the stand group.(P < 0.05).Compared with the Control group,the BS/BV in stand group were decreased,while the Tb.Sp were significant increase.Compared with PBS group,BV/TV,Tb.Th and Tb.N in Exosomes group were increased,while BS/BV and Tb.Sp were decreased.There were significant differences between Exosomes group and PBS group.3.Articular cartilage: compared with the Control group,the positive expression of ACAN and COL II were decreased significantly in the stand group.Compared with PBS group,the positive expression of ACAN and COLII were increased in Exosomes group.Immunofluorescence showed that the number of MMP13 positive cells in the stand group was higher than that in the Control group(P < 0.05).Compared with PBS group,the number of MMP13 positive cells in Exosomes group was decreased(P <0.05).4.Subchondral bone: compared with the Control group,the number of osteoclasts and the positive areas of CD31 and CGRP in the stand group were significantly higher than those in the PBS group.The number of osteoclasts and the positive areas of CD31 and CGRP were decreased in the Exosomes group.Compared with the Control group,the percentage of CD86 positive cells was increased in the stand group,but there was no significant difference in the percentage of CD206 positive cells between Control group and stand group.Compared with PBS group,the percentage of CD206 positive cells was increased and CD86 positive cells was decreased in Exosomes group.Conclusion:The exosomes from human synovial mesenchymal stem cells have protective effect on articular cartilage and cartilage matrix in mice,and can alleviate lumbar facet joints osteoarthritis in mice.