Nanovibrational mesenchymal stem cell stimulation allows detection of highly osteo-specific bioactive metabolites that can be modified for enhanced potency

Interest in bioactive, or activity, metabolites is growing. For adult stem cells in particular, the ability to target desired phenotypes with specificity and potency is important for provision of cellular therapies and also for drug discovery for tissue regeneration. Metabolomics provides a powerful tool for the discovery of bioactive metabolites, but bioinformatic pipelines are hindered by the quality of the input signal that drives the process being studied. For example, with mesenchymal stem cell (MSC) differentiation to bone forming osteoblasts, dexamethasone and bone morphogenetic protein 2 are commonly used stimuli in the lab and in clinic respectively. However, both can result in the artefactual production of adipocytes as well as osteoblasts and this could confound bioactive metabolite identification. Here, we use nanovibrational stimulation of MSCs to promote osteogenesis without adipogenesis and show that this can be used to identify bioactive metabolites with high osteogenic specificity. Further, these metabolites can have their structure-function relationship examined to provide both specificity and enhanced potency as we illustrate within this new work.