Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion

Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion

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Abstract Background Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in VITAMIN C CRYSTALS 1000MG ischemic brain injury, but the underlying mechanism is poorly understood.The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemia.Methods After the intravenous injection of ADSC-EVs, therapeutic efficacy was evaluated by neurobehavioral tests and brain atrophy volume.

The polarization of microglia was assessed by immunostaining and qPCR.We further performed miRNA sequencing of ADSC-EVs and analyzed the relationship between the upregulated miRNAs in ADSC-EVs and microglial polarization-related proteins using Ingenuity Pathway Analysis (IPA).Results The results showed that ADSC-EVs reduced brain atrophy volume, improved neuromotor and cognitive functions after mouse ischemic stroke.

The loss of oligodendrocytes was attenuated after ADSC-EVs injection.The number of blood vessels, as well as newly proliferated endothelial cells in the peri-ischemia area were higher in the ADSC-EVs treated group than that in the PBS group.In addition, ADSC-EVs regulated the polarization of microglia, resulting in increased repair-promoting M2 phenotype and decreased pro-inflammatory M1 phenotype.

Finally, STAT1 and PTEN were highlighted as two downstream targets of up-regulated miRNAs in ADSC-EVs among 85 microglia/macrophage polarization related proteins by IPA.The inhibition of STAT1 and PTEN by ADSC-EVs were confirmed in cultured microglia.Conclusions In summary, ADSC-EVs reduced GLUTEN RELIEF 375 MG ischemic brain injury, which was associated with the regulation of microglial polarization.

miRNAs in ADSC-EVs partly contributed to their function in regulating microglial polarization by targeting PTEN and STAT1.