Piezoelectric cold atmospheric plasma modulates neurogenic cell proliferation and differentiation via cross-signaling

Cold atmospheric plasma regulates cell fate by modulating cellular oxidative stress levels, making it a promising new therapy in the field of cell bioengineering. While the regulatory effects and potential molecular mechanisms of the novel piezoelectric cold atmospheric plasma (Piezo-CAP, PiezoBrush PZ3 handheld device, Relyon Plasma, Germany) on the fate of neurogenic cells remain unclear. We utilized C17.2 neural stem cells, rat astrocytes, and SH-SY5Y neuroblastoma cells to evaluate the impact of Piezo-CAP on cell proliferation, apoptosis, and differentiation through CCK-8 assay, Calcein AM/PI double staining, immunofluorescence, and western blot techniques. The signal network of Piezo-CAP governing neurogenic cell proliferation and differentiation was thoroughly examined by the merging of RNA sequencing and bioinformatics analysis. The results demonstrated that Piezo-CAP has a dual regulatory influence on neurogenic cell fate, dependent on specific parameters and cell types. Significantly, Piezo-CAP enables the bidirectional differentiation of C17.2 neural stem cells into neurons and glial cells. The described effects are mechanistically associated with the buildup of intracellular reactive oxygen and nitrogen species (RONS) and may be enhanced by the activation of the PI3K/AKT signaling pathway. Transcriptome research further confirms that Piezo-CAP can influence signaling pathways related to the maintenance of pluripotency and differentiation, including JAK-STAT, Wnt, and Hippo signaling. In conclusion, Piezo-CAP, as an effective physical stimulation method, may accurately influence the destiny of neurogenic cells through essential signaling pathways facilitated by RONS, including PI3K/AKT. This research provides actual evidence and innovative strategies for the application of Piezo-CAP in neural therapy and neural tissue engineering.