Objective. Osteoarthritis is characterized by an imbalance in cartilage homeostasis, which could potentially be corrected by mesenchymal stem cell (MSC)-based therapies. However, in vivo implantation of undifferentiated MSCs has led to unexpected results. This study was undertaken to establish a model for preconditioning of MSCs toward chondrogenesis as a more effective clinical tool for cartilage regeneration.Methods. A coculture preconditioning system was used to improve the chondrogenic potential of human MSCs and to study the detailed stages of chondrogenesis of MSCs, using a human MSC line, Kp-hMSC, in commitment cocultures with a human chondrocyte line, hPi (labeled with green fluorescent protein [GFP]). In addition, committed MSCs were seeded into a collagen scaffold and analyzed for their neocartilage-forming ability.Results. Coculture of hPi-GFP chondrocytes with Kp-hMSCs induced chondrogenesis, as indicated by the increased expression of chondrogenic genes and accumulation of chondrogenic matrix, but with no effect on osteogenic markers. The chondrogenic process of committed MSCs was initiated with highly activated chondrogenic adhesion molecules and stimulated cartilage developmental growth factors, including members of the transforming growth factor  superfamily and their downstream regulators, the Smads, as well as endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and vascular endothelial growth factor. Furthermore, committed Kp-hMSCs acquired neocartilageforming potential within the collagen scaffold. Osteoarthritis (OA), one of the most common musculoskeletal diseases, has been ascribed to an imbalance in cartilage homeostasis in the aging process (1,2). Hyaline cartilage has little capacity for self-repair. As a result, continuous mechanical stress can lead to the degradation of articular cartilage, culminating in a vicious cycle of destructive processes (3). Many therapeutic interventions directed at the restoration of the reparative capacity of chondrocytes have been explored (3-5). One of the emerging approaches is cell-based therapy, in which expanded chondrocytes are used for cartilage repair. However, the outcome of this approach has been disappointing, due to the difficulties in maintaining chondrocytic phenotypes and the decrease in proliferative capacity of autologous chondrocytes with increasing age (1,6,7).
Conclusion. These findings help define the molecular markers of chondrogenesis and more accuratelyCell therapy based on autologous mesenchymal stem cells (MSCs), which have a vast proliferative ca-
