Effect of bone marrow mesenchymal stem cell-derived exosomes combined with transforming growth factor beta 1 on macrophages

Song Puzhen; Ma Hebin; Chen Hongguang; Zhang Yadong

doi:10.12307/2026.520

Abstract：BACKGROUND:Osteoarthritis is a degenerative disease caused by multiple factors.Studies have found that macrophage polarization plays an important role in osteoarthritis.M1 macrophages release pro-inflammatory factors to promote the development of osteoarthritis,while M2 macrophages produce anti-inflammatory factors to inhibit the development of osteoarthritis. OBJECTIVE:To investigate the effect of bone marrow mesenchymal stem cell-derived exosomes combined with transforming growth factor β1 on the polarization of macrophages,and explore a new method for the treatment of osteoarthritis. METHODS:Bone marrow mesenchymal stem cell-derived exosomes were extracted by differential centrifugal method and identified by transmission electron microscopy,particle size analysis,and western blot assay.Macrophages were treated with bone marrow mesenchymal stem cell-derived exosomes,transforming growth factor β1,and bone marrow mesenchymal stem cell-derived exosomes+transforming growth factor β1 for 24 hours.The macrophages without intervention were used as the control group.The distribution of bone marrow mesenchymal stem cell-derived exosomes in macrophages was observed by confocal microscopy.The effect of macrophage polarization was evaluated by reverse transcription-polymerase chain reaction,enzyme-linked immunosorbent assay,and western blot assay. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cell-derived exosomes were crescent-shaped,with average particle size of about 115 nm.Bone marrow mesenchymal stem cell-derived exosomes expressed the specific protein CD63.(2)Compared with the control group,the expressions of anti-inflammatory factors interleukin-10 and CD163 increased in the other three groups,and the expressions of pro-inflammatory factors interleukin-6 and interleukin-1β decreased,and the effects of bone marrow mesenchymal stem cell-derived exosomes+transforming growth factor β1 group were the most significant(P<0.001).The results show that the combination of bone marrow mesenchymal stem cell-derived exosomes and transforming growth factor β1 more effectively promotes the polarization of M1-type macrophages to M2-type macrophages.