When aged mice are treated with extracellular vesicles derived from human stem cells through the nose, there is a reduction in brain inflammation markers, lower levels of oxidative stress, increased...
Mechanism
Synthesis from 1 study
Stem cell packages sprayed into the nose reach brain immune cells and turn off two harmful signals that cause inflammation and damage in aging brains. This lets the brain’s energy systems recover, protects nerve connections, and helps memory work better.
Most probable mechanism
Tiny packages from stem cells, sprayed into the nose, travel to the brain and enter immune cells there. These packages carry special molecules that block two harmful signaling systems in the immune cells, which are overactive in aging brains. When these systems are turned down, the immune cells stop releasing damaging chemicals and produce less stress on brain cells. This lets the brain’s energy factories work better, protecting connections between nerve cells. As a result, the brain can remember things and recognize objects more like a younger brain.
hiPSC-NSC-EVs are taken up by microglia in the hippocampus after intranasal delivery
miR-30e-3p from EVs binds to NLRP3 mRNA, suppressing translation of NLRP3 protein and preventing inflammasome assembly
miR-181a-5p from EVs binds to STING mRNA, suppressing translation of STING protein and inhibiting downstream TBK1-IRF3 signaling
Inhibition of NLRP3 and cGAS-STING pathways reduces caspase-1 activation, IL-1β/IL-18 secretion, and IFN-α production
Reduced inflammatory signaling lowers oxidative stress markers (MDA, PC) and increases antioxidant defenses (NRF2, SOD)
Lower oxidative stress and inflammation restore expression of nuclear-encoded mitochondrial respiratory chain genes (e.g., Ndufs6, Sdha, Cox4i2)
Improved mitochondrial function enhances ATP production and reduces mitochondrial ROS leakage
Preserved neuronal and synaptic integrity enables normal performance in recognition and spatial memory tasks
Evidence from Studies
Supporting (1)
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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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