Regulation of mesenchymal cell differentiation and biological cartilage repair using cell supplementation

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We have identified BMP signal related factor, SF3b4, and also Gas6. These factors regulated chondrogenic differentiation of undifferentiated mesenchymal cells. We, then analyzed the effect of differentiation-regulated mesenchymal cells on the degenerated cartilage in vitro and demonstrated that the cells could attach and embedded into surface matrix. To further extend the cell-based therapy to the cartilage repair, we have attempted scaffold-free transplantation of large numbers of chondrocytic cells ; cell supplementation by intra-articular injection. A full-thickness articular cartilage defect was created in the femoral patellar groove of the nude rat. N1511 cells with undifferentiated chondroprogenitor phenotype were used for cell supplementation. N1511 cells were treated with bone morphogenetic protein (BMP)/insulin to induce chondrogenic differentiation. Undifferentiated N1511 cells or BMP/insulin treated chondrocytic N1511 cells were briefly labeled with fluorescent dye and a aliquot of 1x107/ml of cells was injected into the knees. Localization of the injected cells and the repair of the defect were evaluated histologically by 18 weeks. Injected cells were mostly attached to the synovial surface and then engrafted into sub-synovial tissue. The cells were also scattered among the repaired tissue that filled the osteochondral defect, whereas they were not detected on the surface of normal articular cartilage. There was no histological evidence of synovial inflammation or ectopic chondroplasia. Spontaneous hyaline regeneration of the defect was not observed in the controls without cell injection. However, intra-articular cell injection enhanced the repair of the defect and BMP/insulin-treated chondrocytic N1511 cells showed better cartilage repair than undifferentiated N1511 cells. Thus, intra-articular supplementation of committed chondrocytic cells may be a potential cell-based therapy for articular cartilage lesions.