NsPEFs-enriched ADSCs-EVs alleviate osteoarthritis via RSPO3-mediated dual pro-chondrogenic and pro-M2 macrophage properties.

ABSTRACT: Osteoarthritis (OA) remains a debilitating joint disorder due to the lack of disease-modifying therapies that can simultaneously halt cartilage degradation and modulate the aberrant immune microenvironment. This study demonstrated the therapeutic potential of extracellular vesicles derived from adipose-derived stem cells preconditioned with nanosecond pulsed electric fields (NsPEFs-ADSCs-EVs). Administration of NsPEFs-ADSCs-EVs significantly attenuated OA progression, as indicated by alleviated cartilage degradation, and a marked shift in synovial macrophage from the pro-inflammatory M1 to the pro-reparative M2 phenotype. Mechanistically, we discovered that NsPEFs-ADSCs-EVs, via surface-enriched ITGA4, activated the PI3K/Akt pathway to instruct the increased secretion of R-spondin 3 (RSPO3

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12856188 | biostudies-literature | 2026 May

REPOSITORIES: biostudies-literature