Extracellular Vesicles from Human Urine-Derived Stem Cells Ameliorate Particulate Polyethylene-Induced Osteolysis

来自人类尿液干细胞的细胞外囊泡可改善颗粒聚乙烯诱导的骨溶解

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作者:Hui Li #, Xiao-Lei Fan #, Yi-Nan Wang, Wei Lu, Haoyi Wang, Runzhi Liao, Min Zeng, Jun-Xiao Yang, Yihe Hu, Jie Xie

Conclusion

Based on our findings, USC-EVs prevent UHMWPE particle-induced osteolysis by decreasing inflammation, suppressing bone resorption and promoting bone formation.

Methods

USCs were characterized by measuring induced multipotent differentiation and flow cytometry. USC-EVs were isolated and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and Western blotting. RAW264.7 cells and bone marrow mesenchymal stem cells (BMSCs) were cultured with USC-EVs to verify osteoclast differentiation and osteoblast formation, respectively, in vitro. The effects of USC-EVs were investigated on a UHMWPE particle-induced murine calvarial osteolysis model by assessing bone mass, the inflammatory reaction, and osteoblast and osteoclast formation.

Purpose

Wear debris particle-induced periprosthetic osteolysis is a severe complication of total joint replacement that

Results

USCs differentiated into osteogenic, adipogenic and chondrogenic cells in vitro and were positive for CD44, CD73, CD29 and CD90 but negative for CD34 and CD45. USC-EVs exhibited a cup-like morphology with a double-layered membrane structure and were positive for CD63 and TSG101 and negative for calnexin. In vitro, USC-EVs promoted the osteogenic differentiation of BMSCs and reduced proinflammatory factor production and osteoclastic activity in RAW264.7 cells. In vivo, local injection of USC-EVs around the central sites of the calvaria decreased inflammatory cytokine generation and osteolysis compared with the control groups and significantly increased bone formation.

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