Engineered PMN-MDSCs-derived exosomes delay the progression of collagen-induced arthritis in mice
Objective:To make engineered exosomes(Ex)derived from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)by electroporation,and evaluate the intervention effect on the progression of collagen-induced arthritis(CIA)mice model.Methods:Firstly,PMN-MDSCs were selected using magnetic beads from CIA mice,and PMN-Ex were prepared in the culture supernatant using ultrafiltration technology combined with reagent precipitation method.The surface marker proteins were detected by Western blotting.The PMN-Ex were modified by electroporation technology.The loading efficiency of miR-93-5p in PMN-Ex was detected by fluorescence quantitative PCR.The modified PMN-Ex were added to regulate the differentiation of Th17 cells.After injecting different PMN-Ex into the CIA mice,the appearance of the toes,the HE staining section of the toes,the mean arthritis index(MAI),the proportion of Th17,and serum IL-17A level in mice were observed.Results:PMN-Ex were prepared successfully.The fluorescence quantitative PCR results showed that the expression level of miR-93-5p in PMN-Ex in the experimental group was significantly higher than that in the negative control group.Compared to the negative control group,the mice treated in the experimental group had mild toe redness and swelling and more complete joint structure.In addition,the proportion of Th17 cells in popliteal lymph node,and serum IL-17A level were significantly reduced.Conclusion:The miR-93-5p mimics-engineered PMN-Ex can alleviate the development of CIA mice more effectively.