Investigating leukaemic stem cell opportune remodeling of the bone marrow microenvironment

Haemopoietic stem cells (HSC) are specialised cells with the ability to renew themselves and produce more stem cells or to mature- a process called differentiation which produces mature blood cells. HSC reside in the bone marrow ‘niche’, a microenvironment, which supports these processes. The progression and development of chronic myeloid leukaemia is encouraged by the establishment of a self-enforcing leukaemic stem cell (LSC) niche, where LSCs remodel the healthy bone marrow niche to their advantage.
To date is has proved difficult to target LSCs with current therapies and to study exactly how LSCs manage to dominate and alter the niche. Recently, using tissue engineering we have developed an artificial niche model, comprising four resident niche cell types; mesenchymal stem cells, HSCs, endothelial cells and osteoblasts. The model is centred around a collagen gel culture, mimicking the bone marrow structure. By utilising this model system, we will provide insight into the microenvironmental changes that LSCs confer and how these changes influence the resident cells.
This niche model will also provide an excellent platform for drug screening in leukaemia. The second phase of the project will concentrate on this aspect, testing current therapies alongside drugs that target pathways involved in LSCs self-renewal.