PROJECT ABSTRACT Osteoarthritis (OA) is a disabling, degenerative disease that involves every tissue in the joint. The inflammatory environment surrounding these tissues is believed to fundamentally underlie OA pathogenesis and may therefore hold a key to treatment. One prominent end result of this dysregulated inflammatory state is long- term, progressive cartilage tissue degradation. Effective disease modifying treatments that can intervene in this degradative cascade are not currently available. Human mesenchymal stem cell (hMSC) injections are emerging as a potential disease modifying treatment for OA due to their multi-faceted immunomodulatory properties. However, hMSC injections suffer from substantial variability in efficacy which can be attributed in part to the inherent complexity of using cells which contain significant population heterogeneity/cell states with varying levels of senescence. We therefore propose: 1) to develop a therapy based on hMSCs enriched for electrical properties associated with superior stemness and immunomodulatory/regenerative capacity and 2) to assess the therapeutic potential of these electrically enriched hMSCs using an in vitro model of early inflammatory OA. We envision that electrical enrichment can be implemented as a novel component of hMSC therapy for combating inflammation and promoting regeneration in OA.