Induced pluripotent stem cell-derived mesenchymal stem cells deliver exogenous miR-105-5p via small extracellular vesicles to rejuvenate senescent nucleus pulposus cells and attenuate intervertebral disc degeneration

Abstract Background Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have emerged as a promising new therapeutic strategy for intervertebral disc degeneration (IVDD). However, the drawbacks of MSCs, including their invasive access, donor age, and limited proliferative capacity, hinder quantity quality MSC-sEVs. Induced pluripotent MSCs (iMSCs) provide an indefinite source with well-defined phenotype function. This study aimed to investigate effect sEVs derived from iMSC (iMSC-sEVs) on IVDD explore underlying molecular mechanisms. Methods models were established by puncturing discs tails rats. Then, iMSC-sEVs injected into punctured discs. The was assessed using MRI HE immunofluorescence staining. age-related phenotypes used determine effects senescent nucleus pulposus cells (NPCs) in vitro. Western blotting detect expression Sirt6. miRNA sequencing analysis find miRNAs that potentially mediate activation Results After intradiscally injecting iMSC-sEVs, NPC senescence significantly improved. could rejuvenate NPCs restore function activating Sirt6 pathway Further, microRNA sequence showed highly enriched miR-105-5p, which played pivotal role iMSC-sEV-mediated downregulating level cAMP-specific hydrolase PDE4D lead activation. Conclusion attenuate development IVDD. exerted anti-ageing delivering miR-105-5p pathway. Our findings indicate iMSCs are MSC candidate obtaining large scale, while avoiding several defects related present applications be novel cell-free tool treatment