BRIGE: Understanding the Mechanical Properties of Migrating Mesenchymal Stem Cells

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This Broadening Participation Research Initiation Grants in Engineering(BRIGE) grant will be used to determine how microscopic mechanical properties contribute to mesenchymal stem cell (MSC) mobility. MSCs are bone marrow-derived adult stem cells that are involved in wound healing and tissue regeneration. In the body, their recruitment to tumor or wound tissues is mediated by soluble proteins often released from hypoxic (oxygen-deprived) tissues. In the lab, MSC treatment with soluble proteins or hypoxia increases MSC migration. The proposed studies will systematically characterize the effects of tumor-secreted soluble proteins and/or hypoxia on the microscopic mechanical properties of MSCs. The mechanical response of a cell to chemical or physical stimuli is regulated by the cytoskeleton, a dynamic network of protein filaments extending throughout the cytoplasm. The cytoskeletal filaments are linked to adhesion molecules in the extracellular environment by focal adhesion complexes. The organization of cytoskeletal filaments and focal adhesion complexes changes rapidly during cell migration. Using quantitative real-time microscopy techniques, including particle tracking microrheology and time-lapsed fluorescent microscopy, the effects of selected stimuli on intracellular rheology, cytoskeletal organization (including cytoskeletal filaments and focal adhesion proteins), and interaction with cell adhesion molecules will be monitored. Together these techniques will be used to identify the mechanical and adhesive properties of migratory MSCs.MSCs are good candidates for the development of cell-based therapeutics. They can be easily harvested from bone marrow, expanded in the lab, genetically manipulated, and differentiated into different types of tissues. However, ex vivo expansion of MSCs alters their morphology limiting their mobility after reinfusion. The studies will provide fundamental information that will be used to optimize the migratory behavior of expanded MSCs. If the research is successful, these studies may provide a new strategy for the delivery of MSC-based therapeutics.