Overview
Topic status: We're looking for students to study this topic.
Mesenchymal stem cells (MSCs) are programmed to differentiate into adipocytes by default; but in the presence of adequate blood supply and appropriate levels of secreted growth factors, they may differentiate into osteoblasts. With age the proportion of yellow bone marrow (measured by adipocyte fraction) increases in bone tissue, replacing the original haemotopoetic or red bone marrow. An age-related decrease in blood vessel number and/or appropriate levels of growth factors may explain changes in the regulation of MSC differentiation with age, which result in increased numbers of adipocytes. Adipocyte fraction is more pronounced in osteoporotic patients compared to age-matched controls, suggesting an important regulatory interaction between bone marrow and bone tissue. Furthermore the location of MSCs and adipocytes appears to play an important role in the cell signalling of bone tissue regulation, in what is termed the haemopoetic niche. The role of bone marrow in bone metastasis is an emerging area of exploration. A relationship between cancer cells and the bone marrow microenvironment may help to explain the bone tissue changes that occur in bone metastasis and provide novel routes of metastatic treatment.
Hypothesis: MSC differentiation is modulated towards an osteoblastic lineage in the presence of CaP cells. As the CaP cells are likely to produce factors that restrict adipocyte differentiation of MSC populations, it is unlikely that adipocytes and CaP cells will co-locate.
Aim 1: Measure adipocyte fraction in the bone marrow of the proximal tibia of SCID mice after the introduction of CaP cells
Aim 2: Measure the functional and structural changes in bone tissue after introduction of CaP cells
Aim 3: Analyse the location of adipocytes, osteoblasts and CaP cells in the bone tissue microenvironment
Methods and techniques that will be developed in the course of this project:
- Small animal surgery
- Cell culture
- Radiography including micro-computerised tomography
- Bone histomorphometry and tissue histology
- Immunohistochemistry
- Study level
- Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisor.
Dr Laura Gregory
Professor Christian Langton
