Abstract
Neuroinflammation develops in neurodegenerative diseases. The severity of neuroinflammation is closely linked to microglial polarization. Different microglial phenotypes release inflammatory cytokines with distinct functions. Modulation of microglial polarization to alter neuroinflammation is a potential therapeutic strategy. Human umbilical cord mesenchymal stem cells (hUCMSCs) possess multiple stem cell properties that can be used to modulate inflammation. Various methods of pre-treatment of stem cells have shown enhanced efficacy in disease treatment. Photobiomodulation (PBM) is a non-invasive intervention that can reduce inflammation. Our in vitro experiments established a microglial cell inflammation model and demonstrated that PBM pre-treated hUCMSCs exhibited reduced the release of pro-inflammatory cytokines while promoting the expression of anti-inflammatory cytokines in microglia. This treatment significantly reduced the expression of Notch pathway-related genes in an inflammatory model, facilitated decreased M1 phenotype polarization, and increased M2 phenotype polarization in microglia. An animal inflammation model was established. In vivo studies showed that 808 nm light combined with hUCMSCs improved memory. and significantly reduced pro-inflammatory cytokines release in serum and brain tissue of male C57BL/6J mice, while promoting the expression of anti-inflammatory cytokines and M2 phenotype polarization of microglia. The results highlight the crucial role of 808 nm PBM in modulating microglial function and attenuating neuroinflammation through interaction with hUCMSCs. The findings offer novel insights into the molecular mechanisms of microglial polarization.