Mesenchymal Stromal Cells in Knee Osteoarthritis: A Review of Nomenclature, Criteria, and Therapeutic Mechanisms

Doo-Ho Lim,1,* Chae-Chil Lee,2,* Ki-Bong Park2 1Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 2Department of Orthopedic Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea*These authors contributed equally to this workCorrespondence: Ki-Bong Park, Department of Orthopedic Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Dong-Gu, Ulsan, Republic of Korea, Tel +82 52 250 7129, Fax +82 52 235 2823, Email [email protected]: Cell-based therapies, particularly utilizing mesenchymal cells, have garnered significant global attention for treating knee osteoarthritis (OA). However, interpreting clinical outcomes remains challenging due to substantial heterogeneity in study designs, cell sources, and preparation methods. This narrative review aims to clarify the evolving nomenclature, outline defining criteria, and elucidate the fundamental mechanisms of these therapies. We highlight the critical scientific transition from “mesenchymal stem cells” to “mesenchymal stromal cells”, an adjustment strongly supported by recent clinical approvals emphasizing immune recalibration over direct tissue regeneration. Currently, robust evidence indicates that mesenchymal stromal cells exert their therapeutic effects primarily through paracrine signaling and immunomodulation, predominantly orchestrated by exosomes, rather than through lineage-driven direct structural repair. Furthermore, we address the practical implications of cell processing—differentiating between minimal manipulation (e.g. cell concentrates) and in vitro expansion—and the stringent regulatory frameworks governing them. Ultimately, standardizing the mechanism-accurate “stromal” terminology and optimizing cell preparation protocols are essential steps for advancing the efficacy and reliability of regenerative treatments in knee OA.Keywords: osteoarthritis, knee, mesenchymal stem cells, exosomes, paracrine communication, regenerative medicine, cell- and tissue-based therapy