Project description:Decreased mineral density is a risk factor for skeletal pathologies including bone metastasis, the leading cause of mortality in patients with advanced breast cancer, but the underlying mechanisms are poorly understood. While reduced mineral density can drive pathological bone remodeling via direct effects on select cell types, indirect effects due to broad changes of the microenvironment may be similarly important. However, how bone mineral content affects microenvironmental heterogeneity remains to be elucidated. Here, we leverage decellularized bone matrices with varied mineral content in combination with single-cell RNA-sequencing to study how reduced bone mineral content affects microenvironmental complexity and tumor growth. We performed single-cell RNA sequencing on implanted decellularized bovine bone scaffolds in which the mineral was either maintained at physiological levels or removed to simulate scenarios of impaired bone mineralization as, for example, present during aging. Using this approach, we explored the heterogeneous stromal response to varied bone mineral content in both an immunocompromised and immunocompetent, syngeneic mouse model in the presence and absence of cancer cells.
Project description:Mineral building materials suffer from weathering processes such as salt efflorescence, freeze-thaw cycling, and microbial colonization. All of these processes are linked to water (liquid and vapor) in the pore space. The degree of damage following these processes is heavily influenced by pore space properties such as porosity, pore size distribution, and pore connectivity. X-ray computed micro-tomography (µCT) has proven to be a valuable tool to non-destructively investigate the pore space of stone samples in 3D. However, a trade-off between the resolution and field-of-view often impedes reliable conclusions on the material's properties. X-ray dark-field imaging (DFI) is based on the scattering of X-rays by sub-voxel-sized features, and as such, provides information on the sample complementary to that obtained using conventional µCT. In this manuscript, we apply X-ray dark-field tomography for the first time on four mineral building materials (quartzite, fired clay brick, fired clay roof tile, and carbonated mineral building material), and investigate which information the dark-field signal entails on the sub-resolution space of the sample. Dark-field tomography at multiple length scale sensitivities was performed at the TOMCAT beamline of the Swiss Light Source (Villigen, Switzerland) using a Talbot grating interferometer. The complementary information of the dark-field modality is most clear in the fired clay brick and roof tile; quartz grains that are almost indistinguishable in the conventional µCT scan are clearly visible in the dark-field owing to their low dark-field signal (homogenous sub-voxel structure), whereas the microporous bulk mass has a high dark-field signal. Large (resolved) pores on the other hand, which are clearly visible in the absorption dataset, are almost invisible in the dark-field modality because they are overprinted with dark-field signal originating from the bulk mass. The experiments also showed how the dark-field signal from a feature depends on the length scale sensitivity, which is set by moving the sample with respect to the grating interferometer.
Project description:Gene expression profile analysis allowed to identify a panel of genes characteristic of silica materials effect on transformation process.