Clinical implementation of stem cell-based cartilage repair techniques has been limited by the inability of these cells to produce cartilaginous tissue equivalent to that produced by native chondrocytes. We have recently shown that while bulk mechanical properties of mesenchymal stem cell (MSC)-laden constructs are lower than chondrocyte-laden constructs, MSCs can in fact produce tissue that matches or exceeds the biochemical and mechanical properties produced by chondrocytes in regions where there is maximal nutrient supply [1]. We also noted that in the central regions of constructs, where nutrient and oxygen availability is lowest (due to consumption through the construct depth), MSC viability was markedly lower than in the outer regions and drastically lower than the center of chondrocyte-laden constructs maintained similarly. These data suggest that MSCs can achieve a high anabolic functionality when they undergo chondrogenesis (via the provision of TGF-β3) and in doing so can produce tissue of equivalent or greater properties than chondrocytes. However, unlike chondrocytes, MSCs appear thrive only when they are provided with a sufficient nutrient supply. To further delineate the role of microenvironmental stressors [2, 3, 4] on MSC viability and functional capacity, we evaluated the impact of glucose and oxygen deprivation, in the presence and absence of TGF-β, during long term culture. Furthermore, since MSC isolation procedures result in a heterogeneous cell population [5,6], we investigated whether different clonal populations respond to these microenvironmental stressors in a distinct fashion.

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