Exosomes derived from bone marrow mesenchymal stem cells attenuate OGD/R-induced apoptosis in PC-12 cells via activation of the PI3K/AKT pathway.

Abstract

Objective: This study aims to investigate the role of exosomes derived from bone marrow mesenchymal stem cell (BMSC) with or without hypoxic precondition (HP) play in ischemic stroke, and the underlying mechanisms.

Methods: Exosomes were characterized by transmission electron microscopy, western blot, and nanoparticle tracking analysis. To simulate neuronal ischemia-reperfusion injury, PC-12 cells underwent oxygen-glucose deprivation followed by reoxygenation (OGD/R). Cell viability and membrane integrity were assessed using CCK-8 and LDH assays, respectively. Apoptosis was evaluated by flow cytometry and TUNEL assay, while the expression of apoptosis-related proteins was analyzed via western blot.

Results: Exosomes derived from BMSC activated the PI3K/Akt signaling pathway and subsequently suppressed apoptosis, thereby ameliorating cellular injury induced by OGD/R. HP enhanced exosome secretion from BMSC; however, it did not significantly alter the particle size distribution of the released exosomes. Notably, when administered at the same concentration, no substantial difference in therapeutic efficacy was observed between exosomes derived from normoxic BMSC and those from HP-treated BMSC. The anti-apoptotic effects conferred by these exosomes were effectively abolished upon treatment with the PI3K inhibitor LY294002, indicating a PI3K/Akt-dependent mechanism.

Conclusions: Exosomes derived frvom BMSC effectively inhibitedp aupoptposis induced by OpGD/R through uactivation of the PI3K/Akt. Although HP significantly enhanced the secretion of exosomes from BMSC, it did not improve the therapeutic efficacy of these exosomes when administered at an equivalent dosage.