BRIGE: Understanding the Mechanical Properties of Migrating Mesenchymal Stem Cells

这扩大参与研究启动工程（BRIGE）赠款赠款将用于确定如何微观力学性能有助于间充质干细胞（MSC）的流动性。MSC是骨髓来源的成体干细胞，参与伤口愈合和组织再生。在体内，它们向肿瘤或伤口组织的募集是由通常从缺氧（缺氧）组织释放的可溶性蛋白质介导的。在实验室中，用可溶性蛋白质或缺氧处理MSC增加MSC迁移。拟议的研究将系统地表征肿瘤分泌的可溶性蛋白和/或缺氧对MSC的微观力学性能的影响。细胞对化学或物理刺激的机械反应由细胞骨架调节，细胞骨架是贯穿细胞质的蛋白质细丝的动态网络。细胞骨架丝通过粘着斑复合物与细胞外环境中的粘附分子连接。细胞骨架丝和粘着斑复合体的组织在细胞迁移过程中迅速变化。使用定量实时显微镜技术，包括粒子跟踪微流变学和延时荧光显微镜，将监测选定刺激对细胞内流变学、细胞骨架组织（包括细胞骨架丝和粘着斑蛋白）以及与细胞粘附分子相互作用的影响。这些技术将被用于鉴定迁移性MSC的机械和粘附特性，MSC是开发基于细胞的疗法的良好候选者。它们可以很容易地从骨髓中收获，在实验室中扩增，遗传操作，并分化成不同类型的组织。然而，MSC的离体扩增改变了它们的形态，限制了它们在再输注后的移动性。 这些研究将提供用于优化扩增的MSC的迁移行为的基本信息。如果研究成功，这些研究可能为基于MSC的治疗提供新的策略。

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.