Extracellular vesicles of ADSCs inhibit ischemic stroke-induced pyroptosis through Gbp3 regulation: A role for the NLRP3/GSDMD signaling pathway.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Mounting data indicates that extracellular vesicles (EVs) have the potential to improve the injury after a stroke. Pyroptosis is a recently identified kind of programmed cell death that initiates an inflammatory reaction. We aimed to ascertain the therapeutic implications and possible molecular processes of EVs obtained from adipose-derived stem cells (ADSCs) in inhibiting pyroptosis in ischemic stroke. Methods The investigation employed transient middle cerebral artery occlusion (tMCAO) rat model and a BV2 of oxygen-glucose deprivation/reoxygenation (OGD/R) to ascertain ADSCs-EVs implications on inflammation and pyroptosis as assessed by neurological deficit scores, TTC staining, IHC, HE, CCK8, WB, ELISA, and immunofluorescence. RNA-Seq was performed on BV2 cells in the control, OGD/R, and OGD/R + ADSCs-EVs groups. Using sequencing data analysis, in the OGD/R group, we screened the upregulated genes regulated by EVs, overlapped with 74 pyroptosis-related genes, and identified Guanylate-binding protein 2 (Gbp2) and Guanylate-binding protein 3 (Gbp3) as key genes. Following the validation of the sequencing results in vivo and in vitro, Gbp3 was selected for further study. To test its regulatory effects on inflammation and pyroptosis, Gbp3 was knocked down and overexpressed in vitro. Results The administration of ADSCs-EVs resulted in a significant reduction in neurolo

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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