Osteoarthritis (OA) is a whole-joint disorder defined by progressive degeneration of articular cartilage, with limited capacity for self-repair. Conventional therapeutic approaches are largely palliative and fail to halt or reverse disease progression. Cell-based therapies, particularly those utilizing mesenchymal stem cells (MSCs), have emerged as a promising regenerative strategy for OA. Despite rapid initial development, the field now confronts significant translational challenges, including variable clinical outcomes, incomplete mechanistic understanding, and a lack of diversity in commercialization pathways. This article systematically evaluates the biological and functional differences among cell sources used in OA therapy, identifies key bottlenecks in clinical translation, and critically examines global and Chinese clinical trial data to reveal an underlying "innovation gap" and the absence of standardized efficacy assessment criteria. To address these issues, we propose a novel "spatiotemporal coordination and multi-axis coupling" mechanistic framework that captures the dynamic interplay between transplanted cells and the pathological joint microenvironment. Finally, we discuss opportunities for deepening scientific insight and fostering innovation in cell therapy for OA, outlining future research directions and advanced application paradigms.