Frustrated by limited availability of cells that are difficult to sustain in culture, investigators have long sought an alternative to chondrocytes for use in generating cells for cartilage repair. This search has led to a comprehensive evaluation of “mesenchymal stem cells”, non-embryonic stem cells recovered in aspirates of bone marrow and other tissues derived from the mesoderm. MSCs indeed possess an avid propensity for chondrogenic differentiation. Marrow and adipose tissue – derived MSCs show promise for generating intact, cellular cartilage in vitro that may be useful for clinical trials. Cultured in diffusion chambers on engineered cellular scaffolds and bio-matrices, these cells allow us to escape the biological and practical limitations that have hindered the development of restorative therapy of osteoarthritis by cartilage and cultured chondrocytes.