Isolation, characterization and potential role in beta cell-endothelium cross-talk of extracellular vesicles released from human pancreatic islets

摘要: The cross-talk between beta cells and endothelium plays a key role in islet physiopathology the revascularization process after transplantation. However, molecular mechanisms involved this are not fully elucidated. Extracellular vesicles (EVs) secreted membrane nanoparticles inter-cellular communication through transfer of proteins nucleic acids. aims study were: 1) isolation characterization EVs from human islets; 2) evaluation pro-angiogenic effect islet-derived on endothelial (IECs). were isolated by ultracentrifugation conditioned medium islets characterized nanotrack analysis (Nanosight), FACS, western blot, bioanalyzer, mRNA/microRNA RT-PCR array. On IECs, we evaluated EV-induced insulin mRNA transfer, proliferation, resistance to apoptosis, vitro angiogenesis, migration, gene protein profiling. sized 236±54 nm, expressed different surface molecules islet-specific (insulin, C-peptide, GLP1R) carried several mRNAs (VEGFa, eNOS) microRNAs (miR-27b, miR-126, miR-130 miR-296) cell function, secretion angiogenesis. Purified internalized into IECs inducing expression, protection apoptosis enhancement Human release biologically active able shuttle specific (miRNAs) target cells. These results suggest putative for cell-endothelium neoangiogenesis which is critical engraftment transplanted islets.