Human platelet lysate-derived extracellular vesicles enhance angiogenesis through miR-126

人血小板裂解物衍生的细胞外囊泡通过 miR-126 增强血管生成

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作者:Antonella Bordin, Maila Chirivì, Francesca Pagano, Marika Milan, Marco Iuliano, Eleonora Scaccia, Orazio Fortunato, Giorgio Mangino, Xhulio Dhori, Elisabetta De Marinis, Alessandra D'Amico, Selenia Miglietta, Vittorio Picchio, Roberto Rizzi, Giovanna Romeo, Fabio Pulcinelli, Isotta Chimenti, Giacomo

Conclusion

PL is a biological source of available EVs with angiogenic effects involving a miRNAs-based cargo. These properties can be exploited for targeted molecular/biological manipulation of PL, by potentially developing a product exclusively manufactured of EVs.

Methods

We tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.

Results

A subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in human umbilical vein endothelial cells (HUVECs) and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched with small RNAs and a high amount of miR-126, the most abundant angiogenic miRNA in platelets. The transfer of miR-126 by EVs in HUVEC after the in vitro inhibition of the endogenous form, restored angiogenesis, without involving VEGF as a downstream target in this system.

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