Analysis of osteo-immune crosstalk during bone healing by longitudinal intravital imaging

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Fracture healing is initiated with an inflammatory phase, during which immune cells invade the damaged tissue area. It is followed by a phase of bone repair. Both processes involve highly dynamic processes on the cellular and subcellular level, such as immune cell migration and cellular interactions between immune and stromal compartments. Intravital microscopy is the method of choice to study these processes, however, analyzing the spatiotemporal aspects of bone regeneration longitudinally has not been possible until now. To overcome this challenge, we have developed a microendoscopic device (LIMB) in the first funding period, allowing to analyze osteo-immune interactions during bone healing in vivo by repeated imaging of the same tissue region in the bone marrow. In the second funding period, we aim to use LIMB to dissect the role of aging on stromal and immune compartments by analyzing their dynamics in different mouse models of fracture healing. The impact of immune cell-derived factors will be tested using conditional knockout mouse strains. Differentiation of immune and mesenchymal cells will be monitored via the analysis of cellular metabolism by microendoscopic fluorescence lifetime imaging. Angiogenesis, which is known to be spatially and mechanistically linked to bone formation, will be analyzed in different age cohorts using LIMB.