MESENCHYMAL CELL-BASED REPAIR OF LARGE, FULL-THICKNESS DEFECTS OF ARTICULAR-CARTILAGE

Osteochondral progenitor cells were used to repair large, full-thickne ss defects of the articular cartilage that had been created in the kne es of rabbits. Adherent cells from bone marrow, or cells from the peri osteum that had been liberated from connective tissue by collagenase d igestion, were grown in culture, dispersed in a type-I collagen gel, a nd transplanted into a large (three-by six-millimeter), full-thickness (three-millimeter) defect in the weight-bearing surface of the medial femoral condyle. The contralateral knee served as a control: either t he defect in that knee was left empty or a cell-free collagen gel was implanted. The periosteal and the bone-marrow-derived cells showed sim ilar patterns of differentiation into articular cartilage and subchond ral bone. Specimens of reparative tissue were analyzed with use of a s emiquantitative histological grading system and by mechanical testing with employment of a porous indenter to measure the compliance of the tissue at intervals until twenty-four weeks after the operation. There was no apparent difference between the results obtained with the cell s from the bone marrow and those from the periosteum. As early as two weeks after transplantation, the autologous osteochondral progenitor c ells had uniformly differentiated into chondrocytes throughout the def ects. This repair cartilage was subsequently replaced with bone in a p roximal-to-distal direction, until, at twenty-four weeks after transpl antation, the subchondral bone was completely repaired, without loss o f overlying articular cartilage. The mechanical testing data were a us eful index of the quality of the long-term repair. Twenty-four weeks a fter transplantation, the reparative tissue of both the bone-marrow an d the periosteal cells was stiffer and less compliant than the tissue derived from the empty defects but less stiff and more compliant than normal cartilage. CLINICAL RELEVANCE: The current modalities for the r epair of defects of the articular cartilage have many disadvantages. T he transplantation of progenitor cells that will form cartilage and bo ne offers a possible alternative to these methods. As demonstrated in this report, autologous, bone-marrow-derived, osteochondral progenitor cells can be isolated and grown in vitro without the loss of their ca pacity to differentiate into cartilage or bone. Sufficient autologous cells can be generated to initiate the repair of articular cartilage a nd the reformation of subchondral bone. The repair tissues appear to u ndergo the same developmental transitions that originally led to the f ormation of articular tissue in the embryo. This approach to the repai r of defects of the articular cartilage may have useful applications i n the repair of large, full-thickness defects of joint surfaces.