GrpE-like 1-engineered synovial mesenchymal stromal cell exosomes: Mechanistic and translational priorities in osteoarthritis

Core Tip

Core Tip: Osteoarthritis still lacks reliable disease-modifying therapies. This review highlights an emerging mitochondria-centered strategy in which synovial mesenchymal stem cell-derived exosomes deliver GrpE-like 1 to engage the phosphatase and tensin homolog-induced kinase 1-dependent mitophagy pathway, improving mitochondrial homeostasis and cartilage outcomes across in vitro and in vivo models. We synthesize the mechanistic rationale and delineate the minimal translational checkpoints required for clinical readiness: Flux-based and specificity-anchored causal validation; chemistry, manufacturing, and controls—including a standardized product definition with mechanism-linked potency assays; and intra-articular pharmacokinetics/pharmacodynamics coupled to biomarker-driven patient stratification.