The bone marrow represents a special tissue environment for tumour cells. In addition to the colonisation of primary bone marrow tumours, it acts as a refuge for various other tumour cells. Tumour cells can colonise the bone marrow, spread and even destroy the bone structure, severely affecting bone function. The niche in the bone marrow, which normally provides the birthplace of haematopoietic cells, also appears to protect metastatic tumour cells from other tissues and can put them into a kind of dormant state in which they can survive for long periods of time and in some cases be reactivated to form metastases. The signals that regulate these processes are unknown, but the bone marrow microenvironment is thought to play a crucial role.
In this project, several new microscopy methods were developed to examine tissue niches in the bone marrow. On the one hand, a method for clearing whole bones has been developed that allows us to analyse the bone marrow in 3D at the single cell level using light sheet fluorescence microscopy. With the help of artificial intelligence (machine learning), individual cells are recognized (segmented) in the images and their localization or position in relation to other cells is quantitatively recorded. In order to dynamically analyse cells in the bone marrow in 3D, we have developed a laser prototype for 3-photon microscopy, which can be used to non-invasively observe cells in the bone marrow of living mice. In addition to cell migration, the dynamics of blood flow can also be analysed. Finally, we have optimised our endoscopy-based longitudinal intravital microscopy system to analyse the metabolism of cells in vivo.
Furthermore, we analysed the localisation of myeloma cells and their microenvironment in the mouse model and found that these cells spread from proximal to distal in the bone marrow. These methods will be helpful in the future for analysing the dynamics and microenvironment of myeloma cells in the bone marrow.