A 3D Graphene Oxide Model Reveals Fine Particulate Matter Induced Cell Cycle Dysregulation in Neural Stem Cells

Fine particulate matter (PM2.5) exposure increases the risk of neurodevelopmental abnormalities by disrupting neural stem cell (NSC) proliferation and cell cycle homeostasis, which are critical for normal neurodevelopment. This study investigated the impact of fine particulate matter (PM2.5) on NSC proliferation and cell cycle using a three-dimensional (3D) graphene oxide (GO) scaffold that mimics the NSC microenvironment. PM2.5 exposure led to concentration-dependent decreases in NSC viability and induced G0/G1 phase arrest via the marked downregulation of Cyclin D1-Cdk4 and Cyclin E-Cdk2, which critically impact G1/S transition. NSCs in 3D GO scaffolds maintained higher expression of key cell cycle regulators (Cyclin A, Cdk1/Cdk2, APC, and Cdc20) and superior cell viability when suffering PM2.5 exposure, demonstrating the 3D culture environment was beneficial for NSC proliferation. We speculate that the 3D culture environment is more favorable and protective for cell proliferation. Therefore, these findings highlight the utility of the 3D GO scaffold for studying PM2.5 effects on growing neural stem cells. This work provides a physiologically relevant in vitro platform that captures microenvironment-dependent neurotoxic responses, consequently offering valuable mechanistic insights into PM2.5-induced developmental neurotoxicity.