In older mice, delivering extracellular vesicles from stem cells through the nose alters gene activity in brain immune cells, increasing expression of genes involved in energy production and stress...
Mechanism
Synthesis from 1 study
Stem cell bubbles sprayed into the nose reach brain immune cells and deliver molecules that turn off harmful inflammation signals and turn on energy-producing genes. This helps the brain’s cleanup crew work better and reduces damage caused by aging.
Most probable mechanism
Tiny bubbles from stem cells, sprayed into the nose, travel to the brain and get absorbed by immune cells there. These bubbles carry special molecules that turn down genes causing inflammation and turn up genes that help the cells produce energy more efficiently. This calms down the overactive immune cells and helps them work better, reducing damage to brain tissue.
hiPSC-NSC-EVs are taken up by hippocampal microglia after intranasal delivery
miR-30e-3p from EVs binds to NLRP3 mRNA, suppressing translation and inhibiting inflammasome assembly
miR-181a-5p from EVs binds to STING mRNA, suppressing translation and blocking downstream IFN signaling
Suppression of NLRP3 and STING pathways reduces caspase-1 activation, IL-1β/IL-18 secretion, and type I interferon production
Reduced inflammatory signaling lowers oxidative stress markers and increases antioxidant gene expression
Lower oxidative stress and inflammation restore expression of nuclear-encoded mitochondrial respiratory chain genes
Upregulated mitochondrial genes enhance electron transport chain function and ATP production
Transcriptomic reprogramming downregulates TLR, MAPK, TNF, and IL-17 signaling pathways in microglia
Evidence from Studies
Supporting (1)
Community contributions welcome
Intranasal Human NSC‐Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS‐STING Signalling, in Aged Hippocampus
Contradicting (0)
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