Epigallocatechin Gallate-Primed Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Endothelial Senescence by Modulating PI3K/AKT/mTOR Signaling and PINK1-Associated Mitochondrial Quality Control

(1) Background: Oxidative stress-induced endothelial senescence is associated with mitochondrial dysfunction, impaired mitochondrial quality control, and pro-inflammatory signaling. We examined whether extracellular vesicles (EVs) derived from epigallocatechin gallate (EGCG)-primed bone marrow mesenchymal stem cells protect senescent human aortic endothelial cells (HAECs). (2) Methods: HAEC senescence was induced with H2O2. EVs from untreated and EGCG-primed BMSCs were isolated and characterized. Proliferation, senescence, apoptosis-associated proteins, mitochondrial morphology and membrane potential, mitophagy-related markers, senescent-HAEC-directed RAW264.7 macrophage migration, and PI3K/AKT/mTOR signaling were evaluated using CCK-8 and EdU assays, senescence-associated β-galactosidase staining, Transwell migration assays, JC-1 staining, transmission electron microscopy, mitochondria–lysosome colocalization, Western blotting, Mdivi-1, PINK1 knockdown, and the PI3K activator 740 Y-P. (3) Results: EGCG-primed BMSC-derived EVs were taken up by HAECs and alleviated H2O2-induced senescence, increasing proliferation. And reducing β-Gal+ cells from 36.47% to 10.17%, and RAW264.7 migration from 720.33 to 123.67. They restored mitochondrial membrane potential, enhanced PINK1/Parkin-associated mitochondrial quality control, and suppressed PI3K/AKT/mTOR phosphorylation. Mdivi-1, PINK1 knockdown, and 740 Y-P attenuated these protective effects relative to the corresponding H2O2 + intervention controls. (4) Conclusions: EGCG priming enhanced the protective activity of BMSC-derived EVs against H2O2-induced endothelial senescence, with the involvement of PI3K/AKT/mTOR inhibition and PINK1-associated mitochondrial quality control.