Glucose Metabolism As a Predictive Tool to Study Chondrogenesis in Human Mesenchymal Stem Cells

Human Mesenchymal Stem Cells (hMSC) are capable of differentiating into a variety of skeletal tissues, making them a promising cell source for cartilage tissue engineering (TE) applications. However, a significant problem with hMSC-based TE cartilage is that no release criteria have been established for further in vivo (or clinical) testing of the resultant tissue. Establishing criteria to predict success/failure of the differentiation will have significant impact, as the quality of hMSC-based cartilage tissue is highly variable and dependent on variables such as culture conditions (media compositions, physical environment such as reactors) and donor-specific biology. Further, such criteria can be a predictive tool for the quality of the tissue; in the case of anticipated failure, they can be used to dynamically intervene, thereby saving resources. In this project, we used glucose uptake as a predictor of the quality of the TE cartilage. The consumption rates of glucose during chondrogenic hMSC aggregate culture over 21 days were examined for individual constructs, in order to relate the dynamic metabolic profiles of differentiating aggregates to their resulting chondrogenesis. We show a distinct metabolic profile when examining cells cultured in chondrogenic media with varying glucose concentrations, and a direct linear relationship between total glucose consumed and magnitude of chondrogenesis as analyzed by quantitative hydroxyproline, glycosaminoglycan results and qualitative histology results. The relationship between glucose consumption rate and quality of chondrogenesis of hMSC aggregates could be used as a predictive tool to study hMSC-chondrogenesis, accelerating studies in the field and helping cartilage TE become a clinically translatable technology.