Human umbilical cord mesenchymal stem cell-derived extracellular vesicles loaded with miR-223 ameliorate myocardial infarction through P53/S100A9 axis

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for myocardial infarction (MI). This study aims to explore the mechanism of human umbilical cord MSCs (hucMSCs)-derived EVs loaded with miR-223 on MI. Inflammation, cell biological functions, and fibrosis in vitro were measured. Furthermore, MI rat models were established to verify the role of EVs-miR-223 in vivo. The binding relationship between miR-223 and P53 was confirmed. ChIP assay was utilized to observe the combination of P53 and S100A9. The suppressed fibrosis of cardiomyocytes occurred with cells overexpressing miR223. MiR-223 contributed to the angiogenesis of HUVECs. P53 was a target gene of miR-223. In vivo, miR223 relieved myocardial fibrosis and inflammation infiltration, and promoted the angiogenesis in MI rats. HucMSC-derived EVs loaded with miR-223 mitigates MI and promotes myocardial repair through the P53/ S100A9 axis, manifesting the underlying therapy values of hucMSC-derived EVs loaded with miR-223 in MI.

Automated summary

This study confirmed the important role of hucMSC-derived EVs loaded with miR-223 in the treatment of MI. MiR-223 can alleviate the pathological process of MI by suppressing fibrosis and promoting angiogenesis, and promote myocardial repair by regulating the P53/S100A9 axis.