This review synthesizes current knowledge on osteoarthritis (OA) and evaluates mesenchymal stem cell‑derived exosomes (MSC‑Exos) as an emerging, cell‑free therapeutic strategy. It begins with an overview of OA epidemiology, risk factors, and the complex pathophysiology that underlies cartilage degradation, synovial inflammation, and subchondral bone changes. The limitations of existing non‑pharmacological, pharmacological, and surgical interventions are discussed, highlighting the unmet need for disease‑modifying treatments. The authors then introduce regenerative medicine concepts, focusing on MSCs and the rationale for using their secreted exosomes. Detailed sections cover exosome biogenesis, surface markers, and the spectrum of isolation and characterization techniques (ultracentrifugation, size‑exclusion chromatography, immuno‑affinity capture). Comparative advantages of MSC‑Exos over whole‑cell therapy—such as lower immunogenicity, easier storage, and reduced tumorigenic risk—are outlined. Various delivery routes are examined, including intra‑articular injection, systemic administration, and incorporation into hydrogels or scaffolds for sustained release. The molecular cargo of MSC‑Exos (miRNAs, lncRNAs, proteins, lipids) and their mechanistic actions on chondrocyte proliferation, extracellular matrix synthesis, macrophage polarization, and inhibition of catabolic pathways (e.g., NF‑κB, MAPK, Wnt) are summarized. Source‑specific differences (adipose, synovial, bone‑marrow, umbilical‑cord, dental‑pulp MSCs) are compared, emphasizing distinct miRNA/protein signatures and therapeutic potency. The review compiles preclinical evidence from rodent and large‑animal OA models, reporting outcomes such as pain reduction, cartilage thickness preservation, and modulation of inflammatory mediators. Early clinical studies are presented, describing safety, dosing regimens, and preliminary efficacy signals. Finally, challenges—including standardization of exosome production, optimal dosing, delivery vehicles, and regulatory pathways—are discussed, and future research directions are proposed.
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Osteoarthritis Overview: Epidemiology, Pathophysiology, and Limitations of Current Therapies
Summarizes the global burden of OA, key risk factors, and the cellular‑molecular mechanisms driving cartilage degradation, synovitis, and subchondral bone remodeling. Reviews non‑pharmacological, pharmacological, and surgical options, emphasizing their limited disease‑modifying capacity and associated adverse‑event profiles.